HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Margolis, D. J. A. Articles by Gambhir, S. S. Search for Related Content PubMed PubMed Citation Articles by Margolis, D. J. A. Articles by Gambhir, S. S.

Molecular Imaging Techniques in Body Imaging¹

¹ From the Department of Radiology, Stanford University School of Medicine, Stanford, Calif (D.J.A.M., R.J.H., R.B.J., A.Q., S.S.G.); Departments of Radiology and Neurology, University of Utah School of Medicine, Huntsman Cancer Institute, 2000 Circle of Hope, Suite 2121, Salt Lake City, UT 84112-5550 (J.M.H.); Department of Bioengineering, Bio-X Program, Stanford University, Stanford, Calif (S.S.G.); and Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, Calif (D.J.A.M.). Received June 27, 2006; revision requested August 30; revision received December 10; accepted January 16, 2007; final version accepted May 1. Address correspondence to J.M.H.

	ABSTRACT

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
Molecular imaging of the body involves new techniques to image cellular biochemical processes, which results in studies with high sensitivity, specificity, and signal-to-background. The most prevalently used molecular imaging technique in body imaging is currently fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET). FDG PET has become the method of choice for the staging and restaging of many of the most common cancers, including lymphoma, lung cancer, breast cancer, and colorectal cancer. FDG PET has also become extremely valuable in monitoring the response to therapeutic drugs in many cancers. New PET agents, such as fluorothymidine and acetate, have also shown promise in the evaluation of response to therapy and in the staging of prostate cancer. Magnetic resonance (MR) spectroscopy has shown promise in the evaluation of prostate cancer. Breast cancer evaluation benefits from advances in spectroscopic imaging and contrast-enhanced kinetic evaluation of vascular permeability, which is altered in neoplastic processes because of release of angiogenic factors. Superparamagnetic iron oxide (SPIO) particles represent the first of an expanding line of MR contrast agents that target specific cellular processes. SPIO particles have also been used in the evaluation of the cirrhotic liver and at MR lymphangiography.

© RSNA, 2007

	INTRODUCTION

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
Anatomic cross-sectional imaging has become the mainstay for the diagnosis of conditions of the body, including those of the neck, thorax, abdomen, and pelvis. The traditional role of molecular body imaging has been to target pathologic or physiologic processes relegated to a few specific diagnoses in nuclear medicine, including thyroid imaging, leukoscintigraphy, gallium scanning, renal function imaging, hepatobiliary function evaluation, and the occasional indium 111 (¹¹¹In) pentetreotide (OctreoScan; Mallinckrodt, Hazelwood, Mo) or iodine 131 metaiodobenzylguanidine (MIBG) study. In the recent past, however, the combination of discoveries in cellular biology and advances in imaging technology has brought molecular imaging to the forefront. These evolving techniques have the potential to be used for many diverse oncologic and inflammatory conditions. Because this is a rapidly growing field, many of the newest advances have not yet received regulatory approval by the Food and Drug Administration; are not yet reimbursed by insurance carriers; and, in some cases, are not yet even optimized for human use. Many of these evolving techniques are available only in university or tertiary medical centers. Many are still investigational and are not available in every country.

Although the majority of modern molecular imaging applications to date involve positron emission tomography (PET) imaging, magnetic resonance (MR) imaging is beginning to have a larger role, in terms of both novel contrast agents and MR spectroscopy. Additionally, there have been some experimental successes with ultrasonographic (US) and optical imaging techniques, although these do not have widespread use in humans to date.

There are a multitude of ways in which molecular imaging can improve staging, restaging, and therapy monitoring in oncology and assist with the evaluation of other nonneoplastic conditions. Molecular targets have been used to develop and design various molecular imaging probes and techniques used today in molecular body imaging (Fig 1). As was discussed in the introductory article in this series (1), there has been an explosion in our basic knowledge of molecular biology. This knowledge will be the basis for the evolution of newer molecular imaging techniques beyond fluorine 18 (¹⁸F) fluorodeoxyglucose (FDG) (chemical name, [¹⁸F]fluoro-2-deoxy-2-D-glucose) PET to include new probes for PET, MR imaging, optical imaging, and US that will allow for characterization of disease processes in the domain of body imaging. We have already witnessed an explosion in the use of FDG PET in body imaging and the effect that it has had on clinical care. Results of FDG PET and computed tomography (CT) have been compared (Fig 2) for the diagnosis, staging, and depiction of recurrence of several malignancies, as well as for the staging of carcinoma of unknown primary (2).

View larger version (69K): [in this window] [in a new window] [Download PPT slide]   Figure 1a: (a) Diagram of molecular targets relevant to molecular body imaging. (b) Chart to accompany a. CEA = carcinoembryonic antigen, F = fluorine 18, F-DOPA = fluorine dihydroxyphenylalanine, FIAU = fialuridine, FLT = fluorothymidine, Gd = gadolinium, P = pyrophosphate.

View larger version (66K): [in this window] [in a new window] [Download PPT slide]   Figure 1b: (a) Diagram of molecular targets relevant to molecular body imaging. (b) Chart to accompany a. CEA = carcinoembryonic antigen, F = fluorine 18, F-DOPA = fluorine dihydroxyphenylalanine, FIAU = fialuridine, FLT = fluorothymidine, Gd = gadolinium, P = pyrophosphate.

View larger version (23K): [in this window] [in a new window] [Download PPT slide]   Figure 2: Summary of FDG PET sensitivity and specificity compared with those of CT for several malignancies and clinical scenarios (diagnosis, staging, and detection of recurrence). n/a = not available.

The information provided in this article may seem biased toward PET imaging with FDG. However, the clinical reality is that FDG PET is the most commonly used and validated molecular imaging technique in current use. As newer tracers become available, PET imaging will become critical for the assessment of many other biochemical alterations in disease, including proliferation, hypoxia, apoptosis, angiogenesis, multidrug resistance, receptor status, and so forth. Similarly targeted MR imaging probes that help measure and assess many of these same important and relevant biologic and biochemical parameters will also become commonly used in clinical practice.

	NON–SMALL CELL LUNG CANCER

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
Diagnosis and Solitary Pulmonary Nodule Evaluation
FDG PET is the most sensitive noninvasive imaging modality for the evaluation of a solitary pulmonary nodule. A study (3) revealed PET to have a specificity of 77%, sensitivity of 93%, positive predictive value of 72%, and negative predictive value of 94%. However, some authors (4) suggest that in lesions with a high pretest probability, a negative finding on a FDG PET image would likely not change management and is thus of no added value.

Lung nodule dynamic contrast material–enhanced CT is widely available and has high negative predictive value and lower cost compared with those of FDG PET. However, in an analysis of 42 nodules imaged with both FDG PET and dynamic contrast-enhanced CT, FDG PET was found to be preferable to dynamic contrast-enhanced CT because of much higher specificity and only slightly lower sensitivity (5). Both dynamic contrast-enhanced CT and FDG PET are suboptimal for evaluating nodules smaller than 8 mm, and, on the basis of Fleischner Society guidelines, these modalities should be followed by conventional CT except for nodules 4 mm or smaller in patients without increased risk for malignancy, in whom such nodules do not warrant follow-up (6). When tissue diagnosis is indicated, FDG PET can help guide the biopsy location by helping discriminate viable from necrotic tumor (Fig 3). Because of the relatively low specificity of FDG PET, evaluation with the tracer FLT (chemical name, 3'-deoxy-3'-[fluorine 18]fluorothymidine) and PET, which helps assess cellular proliferation, has been suggested as an adjunct, because it appears to show increased uptake only in malignancies (Fig 3) (7).

View larger version (55K): [in this window] [in a new window] [Download PPT slide]   Figure 3a: PET images of non–small cell lung cancer. (a) On this coronal FDG PET projection, tumor in patient's left chest is markedly conspicuous given its avidity for tracer. Liver, spleen, and bone marrow concentrate FDG to a much lesser extent. (b) Coronal FLT PET projection in same patient at same location shows similar uptake by tumor as by liver, but with greater uptake by myeloid elements in bone marrow.

View larger version (81K): [in this window] [in a new window] [Download PPT slide]   Figure 3b: PET images of non–small cell lung cancer. (a) On this coronal FDG PET projection, tumor in patient's left chest is markedly conspicuous given its avidity for tracer. Liver, spleen, and bone marrow concentrate FDG to a much lesser extent. (b) Coronal FLT PET projection in same patient at same location shows similar uptake by tumor as by liver, but with greater uptake by myeloid elements in bone marrow.

Therapy Monitoring
One of the great advantages of molecular imaging is its ability to depict alterations in cellular biochemical processes that may reflect tumor response to therapy far in advance of anatomic changes. Response to chemotherapy can be assessed after only one or two cycles by using FDG PET (15). Results of preliminary studies (16–19) in non–small cell lung cancer with FDG PET have shown the promise of this technique for therapy monitoring. FLT PET may also enable more accurate and rapid assessment of response to cytotoxic therapy because it helps assess cellular proliferation (20,21) and has shown promise in discriminating which patients would respond to therapy prior to its administration, although this is still being evaluated (22,23).

	COLORECTAL CANCER

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
Staging and Restaging
Although there has been some interest in the use of FDG PET in screening for colorectal carcinoma (24), the main use is in staging and, more commonly, restaging of colorectal carcinoma (15,24–27). Sensitivities for the diagnosis of colon carcinoma have been reported to range from 95% to 100%, although specificity remains low, likely relating to physiologic bowel uptake of FDG (2,28). In patients suspected of having recurrence, FDG PET has proved superior to CT for restaging. A prospective study (27) revealed that FDG PET led to changes in management decisions in 59% of patients being evaluated for restaging. In direct comparison to CT, PET is more sensitive for local recurrence (95%: FDG PET vs 65%: CT) and similarly sensitive in the depiction of liver metastasis (98%: FDG PET vs 93%: CT). There may be some added benefit from the addition of PET/CT, with staging and restaging accuracy improved from 78% to 89% (29). However, because of the high number of false-positive findings in patients with no clinical risk factors, this population may not benefit from the use of PET compared with conventional imaging (30).

The spatial resolution provided by using PET limits its ability in staging locally, which includes micrometastases to local lymph nodes (the T and N of the TNM staging criterion). It is also inferior to intraoperative US for the evaluation of hepatic metastasis, although its sensitivity has been variably recorded to be as high as 98% (26). In contradistinction to PET, MR imaging may be the test of choice for the initial staging of rectal carcinoma. Results of multiple studies (31–34) have shown it to be equal to endoluminal US for the evaluation of depth of invasion and to be superior in characterization of nodal status, with accuracies ranging from 66% to 92% for Dukes staging depth of penetration of the primary tumor and from 60% to 90% for lymph node evaluation. However, molecular imaging may further advance the role of MR imaging for staging. Results of one study (35) of multiple abdominopelvic malignancies—26% of which were colorectal cancer—showed 93% sensitivity and 100% specificity with the use of superparamagnetic iron oxide (SPIO) intravenous contrast material, which is taken up by the normal reticuloendothelial system of benign lymph nodes and depresses the T2* signal of benign, but not malignant, lymph nodes.

Therapy Monitoring
FLT PET has been investigated as an adjunct to the staging and restaging of colorectal cancer in combination with FDG PET but has been shown to be relatively insensitive for hepatic metastases and is thus not well suited for restaging (36). However, FLT uptake has been shown to correlate with tumor proliferation and may have prognostic implications for radio- or chemotherapy (37,38). FDG PET results have already been shown to be useful in predicting clinical outcomes, especially when time-activity curves were analyzed by using parametric techniques (39,40). Results of one study (41) showed that patients with a change in the maximum standardized uptake value of 62.5% or higher and a change in total lesion glycolysis of 69.5% or higher had significantly improved disease-specific (P = .08 and .03, respectively) and recurrence-free (P = .02 and .01, respectively) survival. FDG PET is also useful in the evaluation of response to ablative therapy of hepatic metastases, including radiofrequency and cryosurgical ablation and chemoembolization (25,42).

	BREAST CANCER

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
Screening for Breast Cancer in Patients at High Risk
Breast cancer is one of the most intensely studied diseases from a molecular biologic, as well as imaging, standpoint; it has been investigated by using standard radiography, dynamic contrast-enhanced MR imaging, MR spectroscopy, FDG PET, FLT PET, scintigraphy, and optical techniques. Breast cancer remains the most commonly diagnosed cancer and the second leading cause of cancer death in women (8). The standard for screening remains conventional mammography. Neither PET nor scintimammography have been advocated for screening, in large part because of the spatial resolution limitations of both. However, results of a large-scale study (43) have validated the use of dynamic contrast-enhanced breast MR imaging for screening high-risk individuals. Use of dynamic contrast enhancement takes advantage of the leaky microvasculature that results from the release of angiogenic factors from malignant cells, which may be in part related to their increased metabolism. Although this is indirectly molecular imaging inasmuch as it evaluates the tissue effects of molecular substrates rather than identifying the molecular mediators directly, it does illustrate the usefulness of understanding the molecular changes involved in neoplasia. Imaging of different contrast-enhancement curves is facilitated by using colorization software that has already been shown to be useful in distinguishing benign from suspicious lesions and is now commercially available; software simplifies and automates the analysis of breast MR imaging data (Fig 4) (44).

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 4a: (a) Dynamic contrast-enhanced MR image and (b) parametric map of dynamic contrast enhancement of invasive ductal carcinoma (IDC) and fibroadenoma (FA). (a) On this T1-weighted fat-suppressed gadolinium-enhanced sagittal MR image (spectral-spatial pulse with magnetization transfer; repetition time msec/echo time msec, 33/9; flip angle, 50°; matrix, 512 x 192 interpolated to 512 x 512; 64 sections; 1.5–2.0-mm section thickness; 20-cm field of view; and acquisition time, 6 minutes 31 seconds) invasive ductal carcinoma appears spiculated with respect to smoothly marginated fibroadenoma, but the slight degree to which invasive ductal carcinoma enhances more than fibroadenoma is not enough to confidently confer degree of suspicion. (b) Intensity-modulated parametric map of pharmacokinetic parameter K21, which is assumed to be proportional to vascular permeability–surface area product of vascular bed and is modulated by blood flow, shows higher value for invasive carcinoma, denoted by yellow, with lower value for fibroadenoma, denoted by blue. Lower K21 values have been shown to correlate with benignity.

View larger version (132K): [in this window] [in a new window] [Download PPT slide]   Figure 4b: (a) Dynamic contrast-enhanced MR image and (b) parametric map of dynamic contrast enhancement of invasive ductal carcinoma (IDC) and fibroadenoma (FA). (a) On this T1-weighted fat-suppressed gadolinium-enhanced sagittal MR image (spectral-spatial pulse with magnetization transfer; repetition time msec/echo time msec, 33/9; flip angle, 50°; matrix, 512 x 192 interpolated to 512 x 512; 64 sections; 1.5–2.0-mm section thickness; 20-cm field of view; and acquisition time, 6 minutes 31 seconds) invasive ductal carcinoma appears spiculated with respect to smoothly marginated fibroadenoma, but the slight degree to which invasive ductal carcinoma enhances more than fibroadenoma is not enough to confidently confer degree of suspicion. (b) Intensity-modulated parametric map of pharmacokinetic parameter K21, which is assumed to be proportional to vascular permeability–surface area product of vascular bed and is modulated by blood flow, shows higher value for invasive carcinoma, denoted by yellow, with lower value for fibroadenoma, denoted by blue. Lower K21 values have been shown to correlate with benignity.

There are currently no Food and Drug Administration–approved techniques for breast cancer screening other than conventional mammography, but great strides have been made in optical imaging. The four techniques being investigated are transillumination, diffusive optical tomography, optical coherence tomography, and exogenous near-infrared fluorescence imaging. Transillumination has advanced substantially since it was proposed in 1929 (52). By using picosecond (10^–12 second) or femtosecond (10^–15 second) laser pulses, images are produced that show hemoglobin and deoxyhemoglobin distribution on the basis of their differential absorption of red and infrared light, a principle similar to pulse oximetry. Diffusive optical tomography employs technologic and mathematical advances and, depending on the technology used, can result in quantified, three-dimensional maps of absorption, scattering, vascularization, oxygenation, and contrast agent uptake in either fluorescence or absorption mode (53). Optical coherence tomography is similar to US, measuring reflected light instead of sound, and trades poor depth of penetration for near–cellular level resolution (54–56). Fluorescent-labeled molecular probes have become commonplace in benchtop research, and, combined with the previously mentioned techniques, show promise for transition to the bedside (57–62). In addition their usefulness evaluating lesions within the breast, there are some experimental data suggesting their usefulness in sentinel lymph node mapping.

Staging and Restaging
Although MR imaging may appear superior for screening, both dynamic contrast-enhanced MR imaging and PET have shown usefulness in the staging of breast cancer. FDG PET has variable sensitivity and specificity for all breast cancers, ranging between 66% and 96% and 83% and 100%, respectively. However, poor sensitivity has been reported for tubular, lobular, and in situ carcinoma (63–66). FDG PET is somewhat better than MR imaging for depiction of nodal disease in the axilla, with a sensitivity ranging from 79% to 100% and a specificity ranging from 50% to 100%; however, most study results (66–69) do not support its replacement of sentinel node mapping because it is insensitive for micrometastases. PET has been shown to be the most sensitive modality for distant staging, depicting all lesions detected by using CT or radionuclide bone scanning and occasionally depicting otherwise unsuspected lesions (65,70,71). FDG PET is the modality of choice for restaging, having higher sensitivity and specificity than conventional imaging (72–74). FLT PET also shows promise, yielding lower background standardized uptake values (as well as lower average tumor standardized uptake values) and greater conspicuity of mediastinal metastases (75).

MR imaging is superior to conventional mammography and US for the evaluation of the local extent of disease and has superior sensitivity compared with that of PET for diagnosis of the primary lesion (63,76,77). The use of an ultrasmall SPIO contrast agent for lymph node evaluation has also shown promise. In a small study (78) of 20 patients, ultrasmall SPIO particles had a sensitivity of 82%, specificity of 100%, and positive predictive value of 100%. Macromolecular contrast agents, such as gadofosveset trisodium (Vasovist; EPIX Pharmaceuticals, Lexington, Mass) and feruglose, also have higher discriminatory power to differentiate tumor from normal tissue when their kinetics are evaluated (47–50).

Therapy Monitoring
Neoadjuvant chemotherapy, or chemotherapy given preoperatively to potentially downstage primary breast cancer, is becoming a mainstay for the treatment of locally advanced breast cancer, which is defined as a primary tumor greater than 5 cm, inflammatory breast cancer, skin and/or chest wall involvement, or fixed axillary lymph node metastases. Both FDG PET and dynamic contrast-enhanced MR imaging can help predict which patients will respond to preoperative chemotherapy. Changes in contrast uptake kinetics between scans before the initiation of neoadjuvant chemotherapy and scans after initiation of neoadjuvant chemotherapy—and, in some cases, extravascular exchange parameters on the pretherapy scan alone—can help predict response to neoadjuvant chemotherapy, which could spare patients an unnecessary wait before surgery (79–81). FDG PET is also predictive of which patients will respond to neoadjuvant chemotherapy when they are evaluated before and after the first cycle of chemotherapy (63,82–84).

	PROSTATE CANCER

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
Prostate cancer is the most common noncutaneous cancer in men and the third leading cause of cancer death in men (8). However, many prostate cancers are indolent, and only a few result in widespread metastases, which results in a high incidence-to-mortality ratio. In addition to the accurate staging of disease, molecular imaging of prostate cancer has the added goal of differentiating aggressive from indolent cancers at the time of diagnosis. Because of the widespread use of serum prostate-specific antigen monitoring, therapy monitoring is less of an issue, although a decrease in glycolysis at FDG PET (85) has been shown to correlate with response to therapy (86).

Prostate cancer is one of the few exceptions to the rule of the superiority of FDG PET over conventional imaging for staging. Results of multiple studies (87–89) have shown FDG PET to have markedly lower sensitivity for the presence of prostate cancer than CT. This is undoubtedly because of the lack of aggressiveness of prostate cancer and the corresponding decreased level of glycolysis of low-grade prostate cancer, particularly when it is still hormonally sensitive. Even a standard radionuclide bone scan has higher sensitivity for osseous metastases.

Because of this failure of FDG PET in the accurate staging of prostate cancer, there is intense interest in other PET agents, including carbon 11 (¹¹C)–labeled acetate, ¹¹C-labeled methionine, and choline labeled with either ¹¹C or ¹⁸F. Acetate is the precursor to acetyl-CoA, a component of the citric (tricarboxylic) acid cycle, which has been found to have increased activity in malignant cells of epithelial origin (90). Carbon 11 acetate has shown superior sensitivity for detection and staging of primary and metastatic prostate cancer tumors compared with FDG, with sensitivities ranging between 59% and 83% compared with those of the combination of CT, bone scintigraphy, and biopsy. However, there is some overlap between the standardized uptake values of prostate cancer and those of benign prostatic hyperplasia (91–94). Carbon 11 methionine, which is an amino acid, is also effective in the evaluation of prostate cancer. Results of one study (95) showed it to be 72% sensitive for lesions detected at conventional imaging, with the suggestion that the actual sensitivity may be higher because some lesions not colocalized may be necrotic or dormant.

Choline is an essential nutrient and is critical for cellular membrane structure and function. Choline metabolism becomes altered in malignancy. This important nutrient is actively taken up by prostate cancer cells, where it is phosphorylated and integrated into phospholipids at increased levels. Carbon 11 choline has a sensitivity analogous to that of ¹¹C acetate, with sensitivity and specificity for lymph node metastasis detection of 80% and 96%, respectively (92,96–99). The shorter half-life and poorer spatial resolution (owing to the longer positron range) of ¹¹C- compared with ¹⁸F-labeled compounds has stimulated the development of ¹⁸F analogs of choline. Both ¹⁸F fluorocholine and ¹⁸F fluoroethylcholine have been produced efficiently with sensitivity analogous to that of ¹¹C choline for detection of primary and metastatic disease (100–102). Because many of these agents are being evaluated for many different tumor types, such as brain and esophageal tumors, it remains to be seen which agent will make it to market first for widespread clinical use in prostate cancer imaging.

Choline has the advantage of being resolvable (in combination with creatine) at MR spectroscopy. Citrate, a component of the citric acid cycle, is also detectable at MR spectroscopy. The increased choline concentration and decreased total citrate concentration, from increased citric acid cycle activity, can therefore be studied by using MR spectroscopy (103–106). The validity of this approach has been proved with results of in vitro cellular studies, as well as with high-field-strength MR spectra of pathologic samples (105,107). The combination of MR imaging and chemical shift three-dimensional MR spectroscopy results in significant correlation between the estimated and the histologic tumor volume, especially for tumors larger than 0.50 cm³ (108). Because of the proximity of the choline and creatine peaks to the polyamine and spermine peaks in the MR spectra, J techniques such as two-dimensional J-resolved techniques have been used to discriminate these compounds, which also facilitates isolation of the citrate peak because of its strong field strength–dependent coupling (Fig 5) (109,110).

View larger version (93K): [in this window] [in a new window] [Download PPT slide]   Figure 5a: MR spectroscopic data of prostate. (a) Transverse fat-suppressed T2-weighted image (6000/80, FSE-XL with chemical fat saturation, 4.0-mm section thickness, no intersection gap) of prostate, acquired at 3 T, is overlaid with grid representing voxels used for spectroscopy. (b) Spectrographs (spiral trajectory two-dimensional J-resolved spectroscopy; 2000/25–285; matrix, 32 x 32) for each voxel, from 4 to 2 ppm at J(0) line. Citrate is modulated and not well resolved, but a choline peak at 3.2 ppm, a marker of increased cellular turnover and suspicious for carcinoma, is evident just to right of midline. Choline peak is inseparable from creatine peak; thus, peak is labeled cho+cre. (c) Because of the strong coupling of citrate (cit) (spiral trajectory two-dimensional J-resolved spectroscopy; 2000/25–285; matrix, 32 x 32), J(8) line shows resolved citrate, a constituent of benign prostate glandular tissue, in anterior left gland.

View larger version (24K): [in this window] [in a new window] [Download PPT slide]   Figure 5b: MR spectroscopic data of prostate. (a) Transverse fat-suppressed T2-weighted image (6000/80, FSE-XL with chemical fat saturation, 4.0-mm section thickness, no intersection gap) of prostate, acquired at 3 T, is overlaid with grid representing voxels used for spectroscopy. (b) Spectrographs (spiral trajectory two-dimensional J-resolved spectroscopy; 2000/25–285; matrix, 32 x 32) for each voxel, from 4 to 2 ppm at J(0) line. Citrate is modulated and not well resolved, but a choline peak at 3.2 ppm, a marker of increased cellular turnover and suspicious for carcinoma, is evident just to right of midline. Choline peak is inseparable from creatine peak; thus, peak is labeled cho+cre. (c) Because of the strong coupling of citrate (cit) (spiral trajectory two-dimensional J-resolved spectroscopy; 2000/25–285; matrix, 32 x 32), J(8) line shows resolved citrate, a constituent of benign prostate glandular tissue, in anterior left gland.

View larger version (26K): [in this window] [in a new window] [Download PPT slide]   Figure 5c: MR spectroscopic data of prostate. (a) Transverse fat-suppressed T2-weighted image (6000/80, FSE-XL with chemical fat saturation, 4.0-mm section thickness, no intersection gap) of prostate, acquired at 3 T, is overlaid with grid representing voxels used for spectroscopy. (b) Spectrographs (spiral trajectory two-dimensional J-resolved spectroscopy; 2000/25–285; matrix, 32 x 32) for each voxel, from 4 to 2 ppm at J(0) line. Citrate is modulated and not well resolved, but a choline peak at 3.2 ppm, a marker of increased cellular turnover and suspicious for carcinoma, is evident just to right of midline. Choline peak is inseparable from creatine peak; thus, peak is labeled cho+cre. (c) Because of the strong coupling of citrate (cit) (spiral trajectory two-dimensional J-resolved spectroscopy; 2000/25–285; matrix, 32 x 32), J(8) line shows resolved citrate, a constituent of benign prostate glandular tissue, in anterior left gland.

MR imaging may play a dual role in the molecular imaging of the prostate with the advent of SPIO lymphangiography. These nanoparticles have a monocrystalline inverse spinel SPIO core and contain a dense packing of dextrans to prolong their circulation time. The nanoparticles are slowly extravasated from the vasculature into the interstitial space, from which they are transported to lymph nodes, where the lymphotropic superparamagnetic nanoparticles are internalized by macrophages. At MR imaging, this causes shortening of T2 signal in these lymph nodes. However, in lymph nodes where the normal macrophages have been replaced by metastases, these particles are not retained, and no significant change in signal is observed (121). Because of the time needed for the circulating SPIO particles to be internalized by macrophages prior to imaging, the process requires that the patient return 24 hours after administration of the SPIO particles for imaging. Interestingly enough, however, the same SPIO particle administration can be used for dynamic enhancement, given its T1-shortening effect (122).

The future of molecular imaging of the prostate will likely be dominated by more specific contrast agents. Capromab pendetide (ProstaScint; Cytogen, Princeton, NJ), an antibody to prostate-specific membrane antigen labeled with ¹¹¹In, has shown some usefulness in the evaluation of prostate cancer metastases (123). Newer agents are being developed, and this raises the potential of PET/CT or contrast-enhanced MR imaging (124). The anatomic localization afforded with PET/CT is especially well suited to these agents because there may be little or no background activity for anatomic reference.

	LYMPHOMA

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
Diagnosis and Staging
Lymphoma is the most common primary hematopoetic malignancy in the United States (8). Staging of lymphoma is typically done by using the Ann Arbor criteria, which depend on the number of sites of disease involved, the type of involvement (nodal or extranodal), and the distribution of disease. This is important because the choice of chemotherapy and type of radiation therapy for both Hodgkin and non-Hodgkin lymphoma is determined by the stage. Therefore, accurate anatomic localization is of the utmost importance.

FDG PET cannot enable accurate differentiation of lymphoma from other causes of inflammatory lymphadenopathy. FDG PET is also relatively insensitive for low-grade lymphomas, especially mucosa-associated lymphoid tissue lymphoma (125–128). Once the diagnosis is made, however, FDG PET has superior sensitivity and specificity for the staging of lymphoma compared with those of conventional imaging. When FDG PET was used to identify the presence or absence of disease in patients with Hodgkin lymphoma, both during initial staging and during restaging, it was found to be 86% sensitive and 96% specific, while CT was 81% sensitive and 41% specific. In patients with non-Hodgkin lymphoma, the sensitivity and specificity for CT were the same as for patients with Hodgkin lymphoma—81% and 41%, respectively, whereas FDG PET was found to be 89% sensitive and 100% specific for the presence of disease (129). When there is discordance between CT and FDG PET findings, FDG PET findings have been found to be more likely to correlate with histologic findings (130). FDG PET is also more accurate than gallium 67 citrate scanning, with FDG PET results showing 100% sensitivity per patient and per lesion and gallium scanning results showing 80% sensitivity per patient and 72% per lesion (131).

Restaging and Therapy Monitoring in Lymphoma
PET has a sensitivity of 87% and a specificity of 93% for depicting recurrent disease, compared with 93% and 10%, respectively, at CT (Fig 2). In a comparison between FDG PET and all other types of conventional imaging combined (including other nuclear medicine examinations) in which clinical outcome was the reference standard for the follow-up of non-Hodgkin lymphoma, FDG PET had a positive predictive value of 95% and a negative predictive value of 83%, versus 72% and 67%, respectively, at conventional imaging (132). This suggests that FDG PET may be the only imaging study necessary for follow-up in these patients. Unfortunately, FDG PET findings do not help predict outcome uniformly well. FDG PET helped predict complete remission better in patients with moderate risk (stage I–III, no relapse, no more than two different prior therapy regimens) than in patients with high risk, with negative predictive values of 90% versus 50%–67% at conventional imaging (133).

Although FDG PET may be the study of choice for staging and restaging lymphoma, MR spectroscopy has shown some promise for evaluating response to therapy. Results with phosphorus 31 (³¹P) MR spectroscopy have shown that the phosphomonoester-to-nucleotide triphosphate ratio decreased significantly after treatment in complete (P < .001) and partial (P < .05) responders but not in nonresponders (P > .1). In addition, the phosphomonoester-to-nucleotide triphosphate ratio in the pretreatment spectra correlated with the subsequent outcome of treatment, which indicates that phosphomonoester-to-nucleotide triphosphate levels are significant predictors of long-term clinical response and time-to-treatment-failure in non-Hodgkin lymphoma (134).

	CARCINOMA OF UNKNOWN PRIMARY

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
Carcinoma of unknown primary is the 10th most common noncutaneous cancer diagnosis in the United States and carries one of the poorest prognoses (8). These patients are assigned the diagnosis of metastatic cancer of unknown primary site (CUP). CUP represents a heterogeneous group of metastatic tumors for which no primary site can be detected after a thorough medical history, careful clinical examination, and extensive diagnostic work-up. These tumors have been divided according to manifestation into metastatic CUP primarily to the liver or to multiple sites, metastatic CUP to lymph nodes, metastatic CUP of the peritoneal cavity, metastatic CUP to the lungs, metastatic CUP to the bones, metastatic CUP to the brain, metastatic neuroendocrine tumor of unknown primary, and metastatic malignant melanoma of unknown primary. CT is useful for depicting the primary tumor in up to 46% of cases (35% in the abdomen or pelvis) and depicting additional metastases in 65% of cases (135). However, FDG PET depicts a primary tumor in up to 54% of cases and is useful in guiding tissue sampling and choice of therapy (local, locoregional, or systemic) (136–139).

	OTHER CANCERS

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
Melanoma
Melanoma prognosis is predicated on its stage at manifestation. Locally controlled tumors have a far better prognosis. Tumor grade is established at excision, and nodal involvement is evaluated by using sentinel lymph node biopsy. Although spread of extremity lesions is often predictable, the use of sentinel lymph node mapping has shown that a high proportion of head, neck, and trunk melanomas drain to unexpected nodal basins or have drainage to two lymph node basins. In addition, patients with disease in two nodal groups have a worse prognosis than those with disease in one nodal group (140). Results of only a single study (141) have suggested that FDG PET has a sensitivity near that of sentinel lymph node mapping, although it has been shown to have a specificity as high as 97% (142,143).

The main limitation of FDG PET is its insensitivity to very small deposits of tumor (micrometastases), despite melanoma being one of the most FDG-avid tumors known. Results of one study (144) have shown that the median tumor volume per lymph node was 28.3 mm³, whereas for FDG PET to demonstrate disease in regional lymph nodes with 90% sensitivity, a 78-mm³ volume of tumor must be present. FDG PET is more accurate than CT for determination of the presence and extent of metastatic disease—92% sensitive and 90% specific for metastases (145). Results of another study (146) in stage IV metastatic melanoma showed that FDG PET performed only slightly better than conventional imaging at depicting disease. The combination of FDG PET and conventional imaging, however, provided the best sensitivity and accuracy for lesion detection (146). Additionally, when FDG PET is added to CT for the evaluation of patients undergoing initial staging of high-risk primary melanoma, a change in care occurs in up to 90% of patients because unsuspected sites of disease are detected (141).

Head and Neck Cancer
Several studies have compared FDG PET with conventional imaging for detection of the primary tumor, as well as for staging of the neck in head and neck cancer. A study by Sigg et al (147) comparing FDG PET with physical examination and anatomic imaging revealed that FDG PET had better sensitivity, specificity, and diagnostic accuracy than CT in nodal staging (94%, 97%, 96%, respectively, for FDG PET vs 88%, 86%, 87%, respectively, for CT). These values, however, did not reach statistical significance. The authors also concluded that use of FDG PET provided additional important information in 22% of cases and altered the therapeutic plan in 11% of patients. In an older study by Nowak et al (148), the sensitivity and specificity, respectively, of FDG PET in detection of primary tumors were 87% and 67% (those for CT or MR imaging were 67% and 44%) (sensitivity, P < .05); in detection of local recurrence, 86% and 75% respectively (those for CT or MR imaging were 57% and 92%); and in detection of lymph node metastases, 80% and 92% (those for CT or MR imaging were 80% and 84%). As in many of the malignancies discussed previously, in head and neck cancer, PET/CT has been shown to be more accurate than PET alone. In a study by Schoder et al (149), FDG PET/CT had a significantly better accuracy than FDG PET alone (96% vs 90%, P = .03). Results of another study (150) have shown that PET/CT is significantly superior to PET or CT alone for detection of malignancy in the head and neck. In this series, PET/CT had a sensitivity of 98%, a specificity of 92%, and an accuracy of 94% (150).

The early results of nodal staging by using a SPIO contrast agent at MR imaging indicate a sensitivity as high as 96% and a specificity as high as 97% according to nodal group (151–155). The sensitivity and specificity of FDG PET for restaging varies broadly, in large part because of false-positive findings from posttreatment inflammation; a minimum interval of 4 months between cessation of therapy and PET evaluation is recommended to minimize this possibility (156).

Although carcinoma of unknown primary has been addressed previously in this article, it deserves special mention here because cervical lymphadenopathy is a common manifestation. The sensitivity of FDG PET for the detection of the primary lesion has a broad range in the literature, from 25% to 73%, and although there is a wide difference of opinion, FDG PET has shown usefulness in this clinical situation (139,157–163).

Gastroesophageal Cancer
Although FDG PET is useful in the staging of esophageal carcinoma, the combination of CT and endoscopic US has the highest sensitivity for the detection of small paraesophageal lymph nodes. However, the specificity of FDG PET (90%) is higher, and FDG PET has higher accuracy for staging of M1a lymph nodes (164). FDG PET is also more accurate than CT (88% vs 65%) in presurgical staging for the presence of resectable versus nonresectable disease (165). This same study also revealed that, for restaging of esophageal cancer, CT and endoscopy, as well as FDG PET, all depicted every case of local recurrence, although the rate of false-positive findings was higher with PET, especially after balloon dilation. FDG PET was found to be more sensitive but less specific than CT for regional recurrence (92% and 83% vs 83% and 92%, respectively). PET was more sensitive and specific than CT for distant disease (95% and 80% vs 79% and 70%, respectively). A recent report (166) included an evaluation of two patient cohorts. The first cohort was formally enrolled in a phase II clinical trial of preoperative chemoradiation. The second consisted of patients who were deemed eligible for the phase II trial on the basis of results of conventional staging methods (clinical examination, endoscopic US, and CT imaging of the chest and abdomen) but who had FDG PET findings consistent with occult metastatic disease. More than one-third of patients determined to have locally advanced esophageal cancer with conventional staging were upstaged with the use of FDG PET. Despite comparable therapy, upstaging with FDG PET predicted a poor 2-year survival. FDG PET has shown its utility in predicting response and survival to both standard preoperative chemotherapy as well as various chemoradiation regimens in numerous other studies (167–170).

Non–Iodine Concentrating Thyroid Cancer
Imaging with radioiodine remains the main technique for staging and a main component of the treatment of thyroid cancer. However, as thyroid cancer dedifferentiates, it loses its avidity for radioiodine. In a study of 24 patients with elevated thyroglobulin levels and a negative finding on a total-body radioiodine scintigraphic scan, FDG PET was found to be 95% sensitive and 88% accurate for identification of disease sites, and, in 38% of the cases, the discovery of additional sites of disease led to a change in surgical planning (171). A recent review of the literature (172) provides an excellent overview of the topic of the use of FDG PET in well-differentiated thyroid cancer. As has been seen with almost all other cancers, the use of integrated imaging with PET/CT improved diagnostic accuracy and patient management in differentiated thyroid cancer. In a recent report, Palmedo et al (173) showed that integrated PET/CT results changed patient treatment in 48% of patients when compared with standard FDG PET and CT.

Ovarian Cancer
Surgical staging remains the mainstay for ovarian cancer. FDG PET findings correlate well with second-look surgery for restaging in terms of evaluating the progression- and disease-free intervals (174). One study (175) revealed that consensus evaluation of CT with FDG PET staging improved correlation with postoperative staging in 87% of patients, compared with 53% for CT staging alone. FDG PET is also useful for the evaluation of recurrence, with a sensitivity of 80% and a specificity of 100% compared with 55% and 100%, respectively, for conventional imaging and 75% and 100%, respectively, for CA-125 serum levels (176). Results of several studies (177–180) have shown sensitivities ranging from 58% to 91%, and these authors concluded that FDG PET is not adequate for staging of disease and detection of recurrent disease. Other studies (181–184), however, have revealed that FDG PET and FDG PET/CT are superior to conventional imaging and therefore are appropriate imaging studies to use, particularly when there is an elevated serum CA 125 level. FDG PET has potential utility in monitoring response to therapy in advanced-stage ovarian cancer (185).

Testicular Cancer
Although FDG PET is sensitive for testicular cancer, it shows no benefit over CT for primary staging of testicular cancer (186–188). FDG PET appears to be superior to conventional imaging for restaging for testicular cancer, by depicting it sooner and being more sensitive for small lesions (189–191). The specificity and sensitivity, respectively, of FDG PET were 100% and 80% versus 74% and 70% for CT in an investigation of residual tumor after chemotherapy (192). Another prospective study (193) designed to investigate whether FDG PET can help improve the prediction of viable tumor in postchemotherapy seminoma residuals revealed that the specificity of FDG PET is significantly better than that of using a diameter of 3 cm or greater as a threshold for residual disease at CT (193). FDG PET also appears to result in prognostic data in relapse prior to high-dose chemotherapy. In an investigation (194) of relapsed disease, sensitivities and specificities, respectively, for the prediction of failure of high-dose chemotherapy were as follows: PET, 100% and 78%; radiologic monitoring, 43% and 78%; and serum tumor marker, 15% and 100%. As with most other tumor types, inflammatory conditions may result in false-positive results. This is especially true of sarcoidosis, which is FDG avid, and results in patients with sarcoidosis may falsely suggest metastasis (195,196).

Renal Cell Carcinoma
FDG is excreted in the kidney just like glucose, but it is not reabsorbed, which leads to its effective concentration in the kidneys, renal collecting systems, ureters, and bladder. This, along with variable to low uptake, limits its use in the evaluation of renal cell carcinoma to some degree. A recent study (197) revealed that FDG PET was valuable in the characterization of solid renal masses depicted at CT or MR imaging in patients suspected of having or with known malignancies. In this same study, the authors concluded that FDG PET was valuable in primary staging and that its results altered treatment in 30% of patients (197). Another report (198), however, revealed that FDG PET does not offer any advantage over CT for the characterization of renal masses but appeared to be an efficient tool for the detection of distant metastases in renal cancer. For the evaluation of metastases, investigations (199–201) have revealed a wide range of sensitivity, from 60% to 87%, but most specificities were close to 100%. Additionally, a positive finding on a scan is predictive of the presence of disease in suspected metastases (202). Several other molecular imaging–type PET tracers, such as ¹¹C-labeled acetate, are being studied for the assessment of renal function and malignancy (203).

Bladder Cancer
Because FDG quickly finds its way into the urinary excretory system, a detailed evaluation of the bladder, even with irrigation, is precluded. However, it is useful for the detection of local lymphadenopathy and distant metastases (204,205). Because choline is not excreted in the urinary system, it has been investigated as a potential PET agent for the evaluation of bladder cancer and shows promise (206).

Cervical Cancer
FDG PET has shown high sensitivity—as much as 94%–100%—in the detection of cervical cancer and its recurrence (207–213). A limitation of many of these studies was the lack of correlation of histopathologic findings with the results of FDG PET, particularly for women with early stage disease. In a recent report (214) of early stage carcinoma of the cervix, it was found that the sensitivity of FDG PET was 53% and the specificity was 90% for detection of pelvic lymph node metastases.

FDG PET is significantly more accurate than CT or MR imaging in restaging for recurrent cervical cancer, and patients who undergo PET have significantly better 2-year survival than those who do not (215). FDG PET has also shown utility in guiding the radiation therapy field (216). A positive finding on a scan after treatment has been shown to correlate with a 32% cause-specific 5-year survival rate, compared with 80% for a negative finding on a scan (217). One study (218) on comparison of PET with MR imaging revealed that the positive predictive value of FDG PET in the pelvis and paraaortic regions appears sufficient to obviate lymph node sampling; however, sampling is still required to exclude small-volume disease distal to sites of abnormality at FDG PET. MR imaging was found to have insufficient accuracy for nodal staging to affect management.

Pancreatic Adenocarcinoma
FDG PET is more sensitive than helical CT for detection of primary pancreatic adenocarcinoma but does not have spatial resolution sufficient to help determine resectability (219–222). In a recent report (223), integrated PET/CT depicted additional distant metastases not appreciated with conventional imaging, and management was changed in 16% of patients with pancreatic cancer that was deemed resectable after routine staging. These researchers concluded that FDG PET/CT was cost effective. FDG PET shows promise in the assessment of tumor viability, response to therapy, and presence of distant metastases in pancreatic cancer (221,224–226). In fact, the standardized uptake value calculated at FDG PET is a prognostic factor (227–229). FDG PET has been shown to have as high as 98% sensitivity (in a subgroup of 72 of 106 patients with normal serum glucose values) (230) and 93% specificity in another series of 73 patients (231) in differentiation of pancreatic adenocarcinoma from chronic pancreatitis. Although FDG PET has been shown to be useful in depicting adenocarcinoma in the setting of chronic pancreatitis (232), inflammatory conditions can give rise to false-positive results, especially in the acute phase (232).

FDG PET is complementary to CT or MR imaging in detection of recurrent pancreatic cancer (233). This recent study (233) revealed that FDG PET was superior to CT or MR imaging for detection of local and extraabdominal recurrence and that CT or MR imaging was more sensitive for the detection of hepatic metastases.

Small Cell Lung Cancer
The use of FDG PET in small cell lung cancer has some promise in the staging and management of patients (234–240). A complete response by FDG PET indicated longer median time to progression (13.7 months) than no complete response (9.7 months) (235). As with pancreatic adenocarcinoma, a high standardized uptake value correlates with poor outcomes (241). FDG PET may also be useful in localizing small cell lung cancer in patients who manifest with a paraneoplastic syndrome (242).

	DIAGNOSIS AND STAGING OF NEUROENDOCRINE-DERIVED TUMORS

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
Neuroendocrine tumors represent the first class of tumors (except for thyroid tumors) to be targeted with imaging tracers and probes for their specific function rather than for increased metabolism and proliferation. Neuroendocrine tumors, including carcinoid and pancreatic islet cell tumors, are derived from the amine precursor uptake and decarboxylation cell line, and it is this affinity that is exploited in their imaging.

The ¹¹C-labeled serotonin tracer 5-hydroxytryptophan (5-HTP) has been used in the staging of carcinoid tumors (243,244). Carbidopa, which is used to inhibit amino acid decarboxylase activity in peripheral tissues, was also administered to prevent renal excretion. This method was able to help depict small lesions in the pancreas and thorax that were not detectable with any other method, including octreotide scintigraphy, MR imaging, and CT, and there was a greater than 95% correlation between changes in urinary 5-hydroxyindoleacetic acid and changes in the transport rate constant for 5-HTP. In another series (245), all 18 patients, including two with normal urinary 5-hydroxyindoleacetic acid levels, had increased uptake of ¹¹C-labeled 5-HTP in the primary mass. Liver, lymph node, pleural, and skeletal metastases also had increased uptake of 5-HTP. PET could depict more lesions than CT in 10 patients and could depict equal numbers of lesions in the other patients. Tumor visibility was better at PET than at CT because of the high and selective uptake of 5-HTP, with a high tumor-to-background ratio. The copper-64–labeled PET agent 1,4,8,11-tetraazacyclotetradecane-N,N',N",N'''-tetraacetic acid (⁶⁴Cu-TETA-OC) can also be used to depict somatostatin receptor–positive tumors and is superior to ¹¹¹In-pentetic acid-octreotide, except possibly in the lung (246).

Because of the short half life of ¹¹C (20.3 minutes), the tracer L-3,4dihydroxy-6-(18)F-fluoro-phenylalanine (¹⁸F-FDOPA), an analog of L-3,4 dihydroxyphenylalanine (L-DOPA), which is taken up by cells of amine precursor uptake and decarboxylation origin, has been investigated (Fig 6). ¹⁸F-FDOPA is becoming more widely available because of its use in assessing and characterizing various parkinsonian syndromes. One study (247) revealed that for neuroendocrine tumors, ¹⁸F-FDOPA was more accurate (sensitivity, 100%; specificity, 91%) in the detection of skeletal lesions than octreotide scintigraphy or CT but was insensitive (sensitivity, 20%; specificity, 94%) in the lung, ostensibly because of respiratory motion during image acquisition. Octreotide scintigraphy yielded its best results in the liver (sensitivity, 75%; specificity, 100%); however, it was less accurate than PET in all organs (247). However, ¹⁸F-FDOPA PET is less sensitive than FDG PET and standard imaging procedures for the staging of small cell lung cancer (248).

View larger version (89K): [in this window] [in a new window] [Download PPT slide]   Figure 6a: (a) Coronal 18F-FDOPA PET image (b) frontal somatostatin-receptor scintigram, and (c) coronal multisection CT reformation in patient with metastasizing glucagonoma of pancreas. Note extensive liver metastasis with massive enlargement of both liver lobes, particularly left lobe (patient had splenectomy); lymph node metastases in left supraclavicular region and epigastrium; and bone metastasis in lumbar spine. Note better resolution of PET images compared with scintigram. Involved lumbar vertebra is clearly shown at 18F-FDOPA PET (a) but shows only weak uptake on scintigram (arrowhead in b). CT could not enable differentiation between vital tumor in lumbar spine and changes after irradiation. (Reprinted, with permission, from reference 247.)

View larger version (81K): [in this window] [in a new window] [Download PPT slide]   Figure 6b: (a) Coronal 18F-FDOPA PET image (b) frontal somatostatin-receptor scintigram, and (c) coronal multisection CT reformation in patient with metastasizing glucagonoma of pancreas. Note extensive liver metastasis with massive enlargement of both liver lobes, particularly left lobe (patient had splenectomy); lymph node metastases in left supraclavicular region and epigastrium; and bone metastasis in lumbar spine. Note better resolution of PET images compared with scintigram. Involved lumbar vertebra is clearly shown at 18F-FDOPA PET (a) but shows only weak uptake on scintigram (arrowhead in b). CT could not enable differentiation between vital tumor in lumbar spine and changes after irradiation. (Reprinted, with permission, from reference 247.)

View larger version (170K): [in this window] [in a new window] [Download PPT slide]   Figure 6c: (a) Coronal 18F-FDOPA PET image (b) frontal somatostatin-receptor scintigram, and (c) coronal multisection CT reformation in patient with metastasizing glucagonoma of pancreas. Note extensive liver metastasis with massive enlargement of both liver lobes, particularly left lobe (patient had splenectomy); lymph node metastases in left supraclavicular region and epigastrium; and bone metastasis in lumbar spine. Note better resolution of PET images compared with scintigram. Involved lumbar vertebra is clearly shown at 18F-FDOPA PET (a) but shows only weak uptake on scintigram (arrowhead in b). CT could not enable differentiation between vital tumor in lumbar spine and changes after irradiation. (Reprinted, with permission, from reference 247.)

	EVALUATION OF CIRRHOTIC LIVER

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
PET Imaging
FDG PET has variable utility in the evaluation of hepatocellular carcinoma, likely because of the variable amounts of glucose-6-phosphatase activity in these tumors. Despite this biochemical limitation, a study (250) with FDG PET imaging revealed a clinically significant effect in 26 (28%) of 91 patients with hepatocellular carcinoma. In another study (251), ¹¹C acetate, which measures important membrane and lipid biosynthetic processes, was compared with FDG. In the subgroup of patients with hepatocellular carcinoma and multiple lesions, the sensitivity of lesion detection with ¹¹C acetate was 87.3%, whereas the sensitivity of detection with FDG was only 47.3%. Thirty-four percent of lesions had uptake of both tracers, and none of the lesions had a negative finding for both tracers (100% sensitivity with both tracers). In the benign lesions studied, patients with focal nodular hyperplasia showed ¹¹C acetate accumulation greater than that in normal liver. Histopathologic correlation suggested that the well-differentiated hepatocellular carcinoma tumors are better detected by using ¹¹C acetate and poorly differentiated tumors are better detected by using FDG. Another study (252) of 50 consecutive patients with 174 suspected liver lesions evaluated by using FDG PET, US, CT, and MR imaging revealed FDG PET to be more sensitive and specific than all modalities for extrahepatic disease and more sensitive and specific than US and CT, but not MR imaging, for the detection of liver lesions.

MR Imaging
SPIO contrast enhancement and ³¹P spectroscopy have both been used to characterize the cirrhotic liver. SPIO contrast material, which is taken up by the reticuloendothelial system and depresses the signal of normal liver at T2 and T2*-weighted imaging, has been used to increase the conspicuity of liver lesions in cirrhosis (Fig 7). In one comparison of multiphasic CT versus SPIO-enhanced MR imaging, the mean areas under the receiver operating characteristic curves were 0.85 for SPIO-enhanced MR imaging and 0.79 for dual-phase spiral CT (P < .05). The mean sensitivity of SPIO-enhanced MR imaging (70.6%) was significantly higher than that of CT (58.1%, P < .05) (253). SPIO contrast enhancement also increases the conspicuity of tumorous but not benign arterioportal shunts (254). Interestingly, it has been shown that the amount of signal depression is less in cirrhotic livers than in noncirrhotic livers, likely owing to Kupffer cell dysfunction (255,256).

View larger version (145K): [in this window] [in a new window] [Download PPT slide]   Figure 7: SPIO-enhanced MR image of liver. This T2*-weighted transverse image (two-dimensional gradient recalled echo; 139/9.53; flip angle, 30°; section thickness, 6 mm; gap, 0.6 mm; matrix, 256 x 256; bandwidth, 150 Hz/pixel; acquisition time, 4 x 18 seconds) of cirrhotic liver would normally be low in signal intensity from uptake of tracer by reticuloendothelial system, but multiple foci of high signal intensity were pathologically proved to be multiple foci of hepatocellular carcinoma. (Image courtesy of Stefan O. Schoenberg, MD, University of Munich, Munich, Germany.)

	LYMPHANGIOGRAPHY

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
The use of FDG PET to image lymph node metastases and local injection of radiolabeled sulfur colloid for sentinel lymph node mapping are well established and have been described previously in this article. An interesting application with clinical relevance that exploits the presence of reticuloendothelial cells is the intravenous administration of SPIO particles with delayed imaging for assessment of nodal metastases. As in the liver, the normal reticuloendothelial cells phagocytize the SPIO nanoparticles, with a resultant decrease in T2- and T2*-weighted signal. However, lymph nodes infiltrated by cancer do not take up SPIO particles and retain their long T2 signal. These lymph nodes are then conspicuous on T2*-weighted images (Fig 8). This phenomenon has been exploited in head and neck, axillary (for breast cancer), and abdominopelvic lymph node evaluation, although sensitivity and specificity appear to vary by formulation of SPIO particles, with sensitivities ranging from 51% to 100% (35,78,121,152,155,259–264).

View larger version (142K): [in this window] [in a new window] [Download PPT slide]   Figure 8a: MR images of benign and metastatic lymph nodes in prostate cancer. (a) External iliac lymph node (white arrow) at level of prostate (black arrow) and femoral head (arrowhead) appears high in signal intensity on unenhanced T2*-weighted fat-suppressed transverse MR image (300–400/24; flip angle, 20°; number of signals acquired, two; matrix, 160 x 256; 3.0-mm section thickness; no intersection gap). (b) Twenty-four hours after intravenous administration of SPIO particles, reticuloendothelial system in benign lymph node has taken up contrast material, with resultant low signal intensity (arrow). (c) Lymph node enlarged with metastasis (arrow) is conspicuous by size in different patient with same imaging parameters at level of femoral head (arrowhead) and external iliac vessels (*). (d) Lesion (arrow) does not decrease in signal intensity 24 hours after intravenous administration of SPIO particles, because its reticuloendothelial system has been replaced by tumor. (Images courtesy of Mukesh Harisinghani, MD, Massachusetts General Hospital, Boston, Mass.)

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 8b: MR images of benign and metastatic lymph nodes in prostate cancer. (a) External iliac lymph node (white arrow) at level of prostate (black arrow) and femoral head (arrowhead) appears high in signal intensity on unenhanced T2*-weighted fat-suppressed transverse MR image (300–400/24; flip angle, 20°; number of signals acquired, two; matrix, 160 x 256; 3.0-mm section thickness; no intersection gap). (b) Twenty-four hours after intravenous administration of SPIO particles, reticuloendothelial system in benign lymph node has taken up contrast material, with resultant low signal intensity (arrow). (c) Lymph node enlarged with metastasis (arrow) is conspicuous by size in different patient with same imaging parameters at level of femoral head (arrowhead) and external iliac vessels (*). (d) Lesion (arrow) does not decrease in signal intensity 24 hours after intravenous administration of SPIO particles, because its reticuloendothelial system has been replaced by tumor. (Images courtesy of Mukesh Harisinghani, MD, Massachusetts General Hospital, Boston, Mass.)

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 8c: MR images of benign and metastatic lymph nodes in prostate cancer. (a) External iliac lymph node (white arrow) at level of prostate (black arrow) and femoral head (arrowhead) appears high in signal intensity on unenhanced T2*-weighted fat-suppressed transverse MR image (300–400/24; flip angle, 20°; number of signals acquired, two; matrix, 160 x 256; 3.0-mm section thickness; no intersection gap). (b) Twenty-four hours after intravenous administration of SPIO particles, reticuloendothelial system in benign lymph node has taken up contrast material, with resultant low signal intensity (arrow). (c) Lymph node enlarged with metastasis (arrow) is conspicuous by size in different patient with same imaging parameters at level of femoral head (arrowhead) and external iliac vessels (*). (d) Lesion (arrow) does not decrease in signal intensity 24 hours after intravenous administration of SPIO particles, because its reticuloendothelial system has been replaced by tumor. (Images courtesy of Mukesh Harisinghani, MD, Massachusetts General Hospital, Boston, Mass.)

View larger version (153K): [in this window] [in a new window] [Download PPT slide]   Figure 8d: MR images of benign and metastatic lymph nodes in prostate cancer. (a) External iliac lymph node (white arrow) at level of prostate (black arrow) and femoral head (arrowhead) appears high in signal intensity on unenhanced T2*-weighted fat-suppressed transverse MR image (300–400/24; flip angle, 20°; number of signals acquired, two; matrix, 160 x 256; 3.0-mm section thickness; no intersection gap). (b) Twenty-four hours after intravenous administration of SPIO particles, reticuloendothelial system in benign lymph node has taken up contrast material, with resultant low signal intensity (arrow). (c) Lymph node enlarged with metastasis (arrow) is conspicuous by size in different patient with same imaging parameters at level of femoral head (arrowhead) and external iliac vessels (*). (d) Lesion (arrow) does not decrease in signal intensity 24 hours after intravenous administration of SPIO particles, because its reticuloendothelial system has been replaced by tumor. (Images courtesy of Mukesh Harisinghani, MD, Massachusetts General Hospital, Boston, Mass.)

	NONONCOLOGIC APPLICATIONS

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

Sarcoidosis
Sarcoidosis is an inflammatory condition and can thus be localized by using FDG PET (272). Regional glucose metabolism, measured by using FDG PET, may reflect inflammatory disease activity in sarcoidosis in quantitative terms (per gram of lung tissue) and delineate disease distribution (273).

Vulnerable Plaque
Three MR contrast agents have been developed that specifically target fibrin: fibrin-binding gadolinium-labeled peptide (EP-1873; EPIX Medical); gadopentetate dimeglumine-phosphatidylethanolamine; and gadopentetate dimeglumine-bis-oleate (Gateway Specialty Chemicals, St. Louis, Mo) (274–277). These agents can localize to vulnerable plaque and show promise for the prevention of acute coronary syndromes and stroke.

	A LOOK TO THE FUTURE

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 
Molecular imaging is set to revolutionize noninvasive imaging. The combination of CT and PET will allow for specific PET imaging agents that have little or no background signal, yet can still be anatomically localized by fusion with CT images. MR will also benefit from targeted contrast agents, including agents that will enhance spectroscopy and agents that take advantage of chemical exchange–saturation transfer for more sensitive evaluation of metabolites and other aspects of the chemical environment (278–283). Advances in optical imaging will likely see the transition from small-animal to clinical imaging in the near future, advancing beyond breast imaging. Targeted microbubbles may allow US to join MR, PET, and optical imaging as a molecular imaging modality (284,285).

The advent of gene therapy and stem cell therapy provides a novel pathway for molecular imaging, because these cells can be labeled with a molecular marker ex vivo that can then be imaged by using PET, MR imaging, or optical techniques (286,287). One of the most important and clinically relevant roles for molecular imaging will be in early therapeutic response monitoring. As has been described in many sections of this manuscript, FDG PET has already shown tremendous potential in several different malignancies to provide a response assessment that can change patient management. Several reviews (15,288,289) describe the utility of FDG PET in providing an early response assessment in numerous different malignancies. The most notable example for this ability to provide a clinically relevant early response assessment by using FDG PET is in patients being treated with imatinib for gastrointestinal stromal tumor (Fig 9) (290–292).

View larger version (145K): [in this window] [in a new window] [Download PPT slide]   Figure 9a: Transverse images in 45-year-old man with recurrent gastrointestinal stromal tumor of small-bowel mesentery and hepatic metastasis. (a, b) Pretreatment CT scan (a) shows hyperattenuating (87 HU) mesenteric mass (arrows, a) in region of previous surgery corresponding to lesion with markedly increased glucose uptake (arrows, b) on FDG PET scan (b). (c) CT scan obtained 2 months after treatment shows that mass (arrows) has decreased in both attenuation (29 HU) and size. (d) FDG PET scan obtained 2 months after treatment shows no appreciable glucose uptake (arrows). FDG PET can enable earlier prediction of response than conventional anatomic imaging. (Reprinted, with permission, from reference 290.)

View larger version (103K): [in this window] [in a new window] [Download PPT slide]   Figure 9b: Transverse images in 45-year-old man with recurrent gastrointestinal stromal tumor of small-bowel mesentery and hepatic metastasis. (a, b) Pretreatment CT scan (a) shows hyperattenuating (87 HU) mesenteric mass (arrows, a) in region of previous surgery corresponding to lesion with markedly increased glucose uptake (arrows, b) on FDG PET scan (b). (c) CT scan obtained 2 months after treatment shows that mass (arrows) has decreased in both attenuation (29 HU) and size. (d) FDG PET scan obtained 2 months after treatment shows no appreciable glucose uptake (arrows). FDG PET can enable earlier prediction of response than conventional anatomic imaging. (Reprinted, with permission, from reference 290.)

View larger version (146K): [in this window] [in a new window] [Download PPT slide]   Figure 9c: Transverse images in 45-year-old man with recurrent gastrointestinal stromal tumor of small-bowel mesentery and hepatic metastasis. (a, b) Pretreatment CT scan (a) shows hyperattenuating (87 HU) mesenteric mass (arrows, a) in region of previous surgery corresponding to lesion with markedly increased glucose uptake (arrows, b) on FDG PET scan (b). (c) CT scan obtained 2 months after treatment shows that mass (arrows) has decreased in both attenuation (29 HU) and size. (d) FDG PET scan obtained 2 months after treatment shows no appreciable glucose uptake (arrows). FDG PET can enable earlier prediction of response than conventional anatomic imaging. (Reprinted, with permission, from reference 290.)

View larger version (89K): [in this window] [in a new window] [Download PPT slide]   Figure 9d: Transverse images in 45-year-old man with recurrent gastrointestinal stromal tumor of small-bowel mesentery and hepatic metastasis. (a, b) Pretreatment CT scan (a) shows hyperattenuating (87 HU) mesenteric mass (arrows, a) in region of previous surgery corresponding to lesion with markedly increased glucose uptake (arrows, b) on FDG PET scan (b). (c) CT scan obtained 2 months after treatment shows that mass (arrows) has decreased in both attenuation (29 HU) and size. (d) FDG PET scan obtained 2 months after treatment shows no appreciable glucose uptake (arrows). FDG PET can enable earlier prediction of response than conventional anatomic imaging. (Reprinted, with permission, from reference 290.)

	FOOTNOTES

 

Abbreviations: 5-HTP = 5-hydroxytryptophan • FDOPA = L-3,4-dihydroxy-6-(18)F-fluoro-phenylalanine • FDG = fluorine 18 fluorodeoxyglucose • FLT = fluorothymidine • SPIO = superparamagnetic iron oxide

Authors stated no financial relationship to disclose.

	References

TOP ABSTRACT INTRODUCTION NON-SMALL CELL LUNG CANCER COLORECTAL CANCER BREAST CANCER PROSTATE CANCER LYMPHOMA CARCINOMA OF UNKNOWN PRIMARY OTHER CANCERS DIAGNOSIS AND STAGING OF... EVALUATION OF CIRRHOTIC LIVER LYMPHANGIOGRAPHY NONONCOLOGIC APPLICATIONS A LOOK TO THE... References

 

1. Hoffman JM, Gambhir SS. Molecular imaging: the vision and opportunity for radiology in the future. Radiology 2007;244:39–47.[Abstract/Free Full Text]
2. Gambhir SS, Czernin J, Schwimmer J, Silverman DH, Coleman RE, Phelps ME. A tabulated summary of the FDG PET literature. J Nucl Med 2001;42(suppl 5):1S–93S. [Free Full Text]
3. Herder GJ, Golding RP, Hoekstra OS, et al. The performance of (18)F-fluorodeoxyglucose positron emission tomography in small solitary pulmonary nodules. Eur J Nucl Med Mol Imaging 2004;31:1231–1236. [Medline]
4. Line BR, White CS. Positron emission tomography scanning for the diagnosis and management of lung cancer. Curr Treat Options Oncol 2004;5:63–73. [Medline]
5. Christensen JA, Nathan MA, Mullan BP, Hartman TE, Swensen SJ, Lowe VJ. Characterization of the solitary pulmonary nodule: 18F-FDG PET versus nodule-enhancement CT. AJR Am J Roentgenol 2006;187:1361–1367. [Abstract/Free Full Text]
6. MacMahon H, Austin JH, Gamsu G, et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology 2005;237:395–400. [Abstract/Free Full Text]
7. Buck AK, Halter G, Schirrmeister H, et al. Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG. J Nucl Med 2003;44:1426–1431. [Abstract/Free Full Text]
8. Ries L, Eisner M, Kosary C, et al. SEER cancer statistics review, 1975–2001. Bethesda, Md: National Cancer Institute, 2004.
9. Vansteenkiste JF. PET scan in the staging of non-small cell lung cancer. Lung Cancer 2003;42(suppl 1):S27–S37. [CrossRef][Medline]
10. van Tinteren H, Hoekstra OS, Smit EF, et al. Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomised trial. Lancet 2002;359:1388–1393. [CrossRef][Medline]
11. Scott WJ, Shepherd J, Gambhir SS. Cost-effectiveness of FDG-PET for staging non-small cell lung cancer: a decision analysis. Ann Thorac Surg 1998;66:1876–1884. [Abstract/Free Full Text]
12. Halpern BS, Schiepers C, Weber WA, et al. Presurgical staging of non-small cell lung cancer: positron emission tomography, integrated positron emission tomography/CT, and software image fusion. Chest 2005;128(4):2289–2297.[CrossRef][Medline]
13. Shim SS, Lee KS, Kim BT, et al. Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging. Radiology 2005;236(3):1011–1019.[Abstract/Free Full Text]
14. Cerfolio RJ, Ojha B, Bryant AS, Raghuveer V, Mountz JM, Bartolucci AA. The accuracy of integrated PET-CT compared with dedicated PET alone for the staging of patients with nonsmall cell lung cancer. Ann Thorac Surg 2004;78(3):1017–1023. [Abstract/Free Full Text]
15. Kostakoglu L, Goldsmith SJ. 18F-FDG PET evaluation of the response to therapy for lymphoma and for breast, lung, and colorectal carcinoma. J Nucl Med 2003;44:224–239. [Abstract/Free Full Text]
16. Hoekstra CJ, Stroobants SG, Smit EF, et al. Prognostic relevance of response evaluation using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with locally advanced non-small cell lung cancer. J Clin Oncol 2005;23(33):8362–8370.[Abstract/Free Full Text]
17. Hicks RJ, Mac Manus MP, Matthews JP, et al. Early FDG-PET imaging after radical radiotherapy for non-small-cell lung cancer: inflammatory changes in normal tissues correlate with tumor response and do not confound therapeutic response evaluation. Int J Radiat Oncol Biol Phys 2004;60(2):412–418. [CrossRef][Medline]
18. Weber WA, Petersen V, Schmidt B, et al. Positron emission tomography in non-small cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use. J Clin Oncol 2003;21:2651–2657. [Abstract/Free Full Text]
19. Mac Manus MP, Hicks RJ, Matthews JP, et al. Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small cell lung cancer. J Clin Oncol 2003;21:1285–1292. [Abstract/Free Full Text]
20. Yap CS, Czernin J, Fishbein MC, et al. Evaluation of thoracic tumors with 18F-fluorothymidine and 18F-flurodeoxyglucose-positron emission tomography. Chest 2006;129:393–401. [CrossRef][Medline]
21. Mankoff DA, Shields AF, Krohn KA. PET imaging of cellular proliferation. Radiol Clin North Am 2005;43(1):153–167. [CrossRef][Medline]
22. Vansteenkiste JF, Stroobants SG. Positron emission tomography in the management of non-small cell lung cancer. Hematol Oncol Clin North Am 2004;18:269–288. [CrossRef][Medline]
23. Vesselle H, Grierson J, Muzi M, et al. In vivo validation of 3'deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) as a proliferation imaging tracer in humans: correlation of [(18)F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin Cancer Res 2002;8:3315–3323. [Abstract/Free Full Text]
24. Chen YK, Kao CH, Liao AC, Shen YY, Su CT. Colorectal cancer screening in asymptomatic adults: the role of FDG PET scan. Anticancer Res 2003;23:4357–4361. [Medline]
25. Langenhoff BS, Oyen WJ, Jager GJ, et al. Efficacy of fluorine-18-deoxyglucose positron emission tomography in detecting tumor recurrence after local ablative therapy for liver metastases: a prospective study. J Clin Oncol 2002;20:4453–4458. [Abstract/Free Full Text]
26. Rohren EM, Paulson EK, Hagge R, et al. The role of F-18 FDG positron emission tomography in preoperative assessment of the liver in patients being considered for curative resection of hepatic metastases from colorectal cancer. Clin Nucl Med 2002;27:550–555. [CrossRef][Medline]
27. Kalff V, Hicks RJ, Ware RE, Hogg A, Binns D, McKenzie AF. The clinical impact of (18)F-FDG PET in patients with suspected or confirmed recurrence of colorectal cancer: a prospective study. J Nucl Med 2002;43:492–499. [Abstract/Free Full Text]
28. Abdel-Nabi H, Doerr RJ, Lamonica DM, et al. Staging of primary colorectal carcinomas with fluorine-18 fluorodeoxyglucose whole-body PET: correlation with histopathologic and CT findings. Radiology 1998;206:755–760. [Abstract/Free Full Text]
29. Cohade C, Osman M, Leal J, Wahl RL. Direct comparison of (18)F-FDG PET and PET/CT in patients with colorectal carcinoma. J Nucl Med 2003;44:1797–1803. [Abstract/Free Full Text]
30. Schussler-Fiorenza CM, Mahvi DM, Niederhuber J, Rikkers LF, Weber SM. Clinical risk score correlates with yield of PET scan in patients with colorectal hepatic metastases. J Gastrointest Surg 2004;8:150–157; discussion 157–158. [CrossRef][Medline]
31. Gualdi GF, Casciani E, Guadalaxara A, d'Orta C, Polettini E, Pappalardo G. Local staging of rectal cancer with transrectal ultrasound and endorectal magnetic resonance imaging: comparison with histologic findings. Dis Colon Rectum 2000;43:338–345. [CrossRef][Medline]
32. Fuchsjager MH, Maier AG, Schima W, et al. Comparison of transrectal sonography and double-contrast MR imaging when staging rectal cancer. AJR Am J Roentgenol 2003;181:421–427. [Abstract/Free Full Text]
33. Chung HW, Chung JB, Park SW, Song SY, Kang JK, Park CI. Comparison of hydrocolonic sonograpy accuracy in preoperative staging between colon and rectal cancer. World J Gastroenterol 2004;10:1157–1161. [Medline]
34. Schaffzin DM, Wong WD. Endorectal ultrasound in the preoperative evaluation of rectal cancer. Clin Colorectal Cancer 2004;4:124–132. [Medline]
35. Harisinghani MG, Saini S, Weissleder R, et al. MR lymphangiography using ultrasmall superparamagnetic iron oxide in patients with primary abdominal and pelvic malignancies: radiographic-pathologic correlation. AJR Am J Roentgenol 1999;172:1347–1351. [Abstract/Free Full Text]
36. Francis DL, Visvikis D, Costa DC, et al. Potential impact of [18F]3'-deoxy-3'-fluorothymidine versus [18F]fluoro-2-deoxy-D-glucose in positron emission tomography for colorectal cancer. Eur J Nucl Med Mol Imaging 2003;30:988–994. [CrossRef][Medline]
37. Visvikis D, Francis D, Mulligan R, et al. Comparison of methodologies for the in vivo assessment of 18FLT utilisation in colorectal cancer. Eur J Nucl Med Mol Imaging 2004;31:169–178. [CrossRef][Medline]
38. Francis DL, Freeman A, Visvikis D, et al. In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography. Gut 2003;52:1602–1606. [Abstract/Free Full Text]
39. Dimitrakopoulou-Strauss A, Strauss LG, Rudi J. PET-FDG as predictor of therapy response in patients with colorectal carcinoma. Q J Nucl Med 2003;47:8–13. [Medline]
40. Calvo FA, Domper M, Matute R, et al. 18F-FDG positron emission tomography staging and restaging in rectal cancer treated with preoperative chemoradiation. Int J Radiat Oncol Biol Phys 2004;58:528–535. [CrossRef][Medline]
41. Guillem JG, Moore HG, Akhurst T, et al. Sequential preoperative fluorodeoxyglucose-positron emission tomography assessment of response to preoperative chemoradiation: a means for determining longterm outcomes of rectal cancer. J Am Coll Surg 2004;199:1–7. [Medline]
42. Wong CY, Salem R, Raman S, Gates VL, Dworkin HJ. Evaluating 90Y-glass microsphere treatment response of unresectable colorectal liver metastases by [18F]FDG PET: a comparison with CT or MRI. Eur J Nucl Med Mol Imaging 2002;29:815–820. [CrossRef][Medline]
43. Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 2004;351:427–437. [Abstract/Free Full Text]
44. Agoston AT, Daniel BL, Herfkens RJ, et al. Intensity-modulated parametric mapping for simultaneous display of rapid dynamic and high-spatial-resolution breast MR imaging data. RadioGraphics 2001;21:217–226. [Abstract/Free Full Text]
45. Artemov D, Mori N, Ravi R, Bhujwalla ZM. Magnetic resonance molecular imaging of the HER-2/neu receptor. Cancer Res 2003;63:2723–2727. [Abstract/Free Full Text]
46. Artemov D, Mori N, Okollie B, Bhujwalla ZM. MR molecular imaging of the Her-2/neu receptor in breast cancer cells using targeted iron oxide nanoparticles. Magn Reson Med 2003;49:403–408. [CrossRef][Medline]
47. Daldrup-Link HE, Rydland J, Helbich TH, et al. Quantification of breast tumor microvascular permeability with feruglose-enhanced MR imaging: initial phase II multicenter trial. Radiology 2003;229:885–892. [Abstract/Free Full Text]
48. Turetschek K, Floyd E, Helbich T, et al. MRI assessment of microvascular characteristics in experimental breast tumors using a new blood pool contrast agent (MS-325) with correlations to histopathology. J Magn Reson Imaging 2001;14:237–242. [CrossRef][Medline]
49. Turetschek K, Roberts TP, Floyd E, et al. Tumor microvascular characterization using ultrasmall superparamagnetic iron oxide particles (USPIO) in an experimental breast cancer model. J Magn Reson Imaging 2001;13:882–888. [CrossRef][Medline]
50. Turetschek K, Floyd E, Shames DM, et al. Assessment of a rapid clearance blood pool MR contrast medium (P792) for assays of microvascular characteristics in experimental breast tumors with correlations to histopathology. Magn Reson Med 2001;45:880–886. [CrossRef][Medline]
51. Jacobs MA, Barker PB, Bottomley PA, Bhujwalla Z, Bluemke DA. Proton magnetic resonance spectroscopic imaging of human breast cancer: a preliminary study. J Magn Reson Imaging 2004;19:68–75. [CrossRef][Medline]
52. Cutler M. Transillumination as an aid in the diagnosis of breast lesions. Surg Gynecol Obstet 1929;48:721–729.
53. Ntziachristos V, Chance B. Probing physiology and molecular function using optical imaging: applications to breast cancer. Breast Cancer Res 2001;3:41–46. [CrossRef][Medline]
54. Boppart SA, Luo W, Marks DL, Singletary KW. Optical coherence tomography: feasibility for basic research and image-guided surgery of breast cancer. Breast Cancer Res Treat 2004;84:85–97. [CrossRef][Medline]
55. Loo C, Lin A, Hirsch L, et al. Nanoshell-enabled photonics-based imaging and therapy of cancer. Technol Cancer Res Treat 2004;3:33–40. [Medline]
56. Sokolov K, Follen M, Aaron J, et al. Real-time vital optical imaging of precancer using anti-epidermal growth factor receptor antibodies conjugated to gold nanoparticles. Cancer Res 2003;63:1999–2004. [Abstract/Free Full Text]
57. Bremer C, Ntziachristos V, Weissleder R. Optical-based molecular imaging: contrast agents and potential medical applications. Eur Radiol 2003;13:231–243. [Medline]
58. Gurfinkel M, Ke S, Wen X, Li C, Sevick-Muraca EM. Near-infrared fluorescence optical imaging and tomography. Dis Markers 2003;19:107–121. [Medline]
59. Godavarty A, Eppstein MJ, Zhang C, et al. Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera. Phys Med Biol 2003;48:1701–1720. [CrossRef][Medline]
60. Hawrysz DJ, Sevick-Muraca EM. Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents. Neoplasia 2000;2:388–417. [CrossRef][Medline]
61. Godavarty A, Thompson AB, Roy R, et al. Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies. J Biomed Opt 2004;9:488–496. [CrossRef][Medline]
62. Lenkinski RE, Ahmed M, Zaheer A, Frangioni JV, Goldberg SN. Near-infrared fluorescence imaging of microcalcification in an animal model of breast cancer. Acad Radiol 2003;10:1159–1164. [CrossRef][Medline]
63. Walter C, Scheidhauer K, Scharl A, et al. Clinical and diagnostic value of preoperative MR mammography and FDG-PET in suspicious breast lesions. Eur Radiol 2003;13:1651–1656. [CrossRef][Medline]
64. Wahl RL, Cody RL, Hutchins GD, Mudgett EE. Primary and metastatic breast carcinoma: initial clinical evaluation with PET with the radiolabeled glucose analogue 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 1991;179:765–770. [Abstract/Free Full Text]
65. Avril N, Rose CA, Schelling M, et al. Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. J Clin Oncol 2000;18:3495–3502. [Abstract/Free Full Text]
66. Adler LP, Crowe JP, al-Kaisi NK, Sunshine JL. Evaluation of breast masses and axillary lymph nodes with [F-18] 2-deoxy-2-fluoro-D-glucose PET. Radiology 1993;187:743–750. [Abstract/Free Full Text]
67. Wahl RL, Siegel BA, Coleman RE, Gatsonis CG. Prospective multicenter study of axillary nodal staging by positron emission tomography in breast cancer: a report of the staging breast cancer with PET study group. PET Study Group. J Clin Oncol 2004;22(2):277–285. [Abstract/Free Full Text]
68. Crippa F, Agresti R, Seregni E, et al. Prospective evaluation of fluorine-18-FDG PET in presurgical staging of the axilla in breast cancer. J Nucl Med 1998;39:4–8. [Abstract/Free Full Text]
69. Utech CI, Young CS, Winter PF. Prospective evaluation of fluorine-18 fluorodeoxyclucose positron emission tomography in breast cancer for staging of the axilla related to surgery and immunocytochemistry. Eur J Nucl Med 1996;23:1588–1593. [CrossRef][Medline]
70. van der Hoeven JJ, Krak NC, Hoekstra OS, et al. 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography in staging of locally advanced breast cancer. J Clin Oncol 2004;22:1253–1259. [Abstract/Free Full Text]
71. Yang SN, Liang JA, Lin FJ, Kao CH, Lin CC, Lee CC. Comparing whole body (18)F-2-deoxyglucose positron emission tomography and technetium-99m methylene diphosphonate bone scan to detect bone metastases in patients with breast cancer. J Cancer Res Clin Oncol 2002;128:325–328. [CrossRef][Medline]
72. Siggelkow W, Zimny M, Faridi A, Petzold K, Buell U, Rath W. The value of positron emission tomography in the follow-up for breast cancer. Anticancer Res 2003;23:1859–1867. [Medline]
73. Vranjesevic D, Filmont JE, Meta J, et al. Whole-body (18)F-FDG PET and conventional imaging for predicting outcome in previously treated breast cancer patients. J Nucl Med 2002;43:325–329. [Abstract/Free Full Text]
74. Moon DH, Maddahi J, Silverman DH, Glaspy JA, Phelps ME, Hoh CK. Accuracy of whole-body fluorine-18-FDG PET for the detection of recurrent or metastatic breast carcinoma. J Nucl Med 1998;39:431–435. [Abstract/Free Full Text]
75. Smyczek-Gargya B, Fersis N, Dittmann H, et al. PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study. Eur J Nucl Med Mol Imaging 2004;31:720–724. [CrossRef][Medline]
76. Rieber A, Schirrmeister H, Gabelmann A, et al. Pre-operative staging of invasive breast cancer with MR mammography and/or PET: boon or bunk? Br J Radiol 2002;75:789–798.
77. Heinisch M, Gallowitsch HJ, Mikosch P, et al. Comparison of FDG-PET and dynamic contrast-enhanced MRI in the evaluation of suggestive breast lesions. Breast 2003;12:17–22. [CrossRef][Medline]
78. Michel SC, Keller TM, Frohlich JM, et al. Preoperative breast cancer staging: MR imaging of the axilla with ultrasmall superparamagnetic iron oxide enhancement. Radiology 2002;225:527–536. [Abstract/Free Full Text]
79. Martincich L, Montemurro F, De Rosa G, et al. Monitoring response to primary chemotherapy in breast cancer using dynamic contrast-enhanced magnetic resonance imaging. Breast Cancer Res Treat 2004;83:67–76. [CrossRef][Medline]
80. Wasser K, Klein SK, Fink C, et al. Evaluation of neoadjuvant chemotherapeutic response of breast cancer using dynamic MRI with high temporal resolution. Eur Radiol 2003;13:80–87. [Medline]
81. Hayes C, Padhani AR, Leach MO. Assessing changes in tumour vascular function using dynamic contrast-enhanced magnetic resonance imaging. NMR Biomed 2002;15:154–163. [CrossRef][Medline]
82. Gennari A, Donati S, Salvadori B, et al. Role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early assessment of response to chemotherapy in metastatic breast cancer patients. Clin Breast Cancer 2000;1:156–161; discussion 162–163. [Medline]
83. Krak NC, van der Hoeven JJ, Hoekstra OS, Twisk JW, van der Wall E, Lammertsma AA. Measuring [(18)F]FDG uptake in breast cancer during chemotherapy: comparison of analytical methods. Eur J Nucl Med Mol Imaging 2003;30:674–681. [Medline]
84. Mankoff DA, Dunnwald LK, Gralow JR, et al. Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy. J Nucl Med 2003;44:1806–1814. [Abstract/Free Full Text]
85. Kelloff GJ, Hoffman JM, Johnson B, et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res 2005;11(8):2785–2808.[Abstract/Free Full Text]
86. Macapinlac HA, Humm JL, Akhurst T, et al. Differential metabolism and pharmacokinetics of L-[1-(11)C]-methionine and 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) in androgen independent prostate cancer. Clin Positron Imaging 1999;2(3):173–181. [CrossRef][Medline]
87. Sung J, Espiritu JI, Segall GM, Terris MK. Fluorodeoxyglucose positron emission tomography studies in the diagnosis and staging of clinically advanced prostate cancer. BJU Int 2003;92:24–27. [CrossRef][Medline]
88. Salminen E, Hogg A, Binns D, Frydenberg M, Hicks R. Investigations with FDG-PET scanning in prostate cancer show limited value for clinical practice. Acta Oncol 2002;41:425–429. [CrossRef][Medline]
89. Oyama N, Akino H, Suzuki Y, et al. FDG PET for evaluating the change of glucose metabolism in prostate cancer after androgen ablation. Nucl Med Commun 2001;22:963–969. [CrossRef][Medline]
90. Costello LC, Franklin RB. Citrate metabolism of normal and malignant prostate epithelial cells. Urology 1997;50:3–12. [CrossRef][Medline]
91. Oyama N, Miller TR, Dehdashti F, et al. 11C-acetate PET imaging of prostate cancer: detection of recurrent disease at PSA relapse. J Nucl Med 2003;44:549–555. [Abstract/Free Full Text]
92. Kotzerke J, Volkmer BG, Glatting G, et al. Intraindividual comparison of [11C]acetate and [11C]choline PET for detection of metastases of prostate cancer. Nuklearmedizin 2003;42:25–30. [Medline]
93. Fricke E, Machtens S, Hofmann M, et al. Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients. Eur J Nucl Med Mol Imaging 2003;30:607–611. [Medline]
94. Kato T, Tsukamoto E, Kuge Y, et al. Accumulation of [11C]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer. Eur J Nucl Med Mol Imaging 2002;29:1492–1495. [CrossRef][Medline]
95. Nunez R, Macapinlac HA, Yeung HW, et al. Combined 18F-FDG and 11C-methionine PET scans in patients with newly progressive metastatic prostate cancer. J Nucl Med 2002;43:46–55. [Abstract/Free Full Text]
96. de Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJ. 11C-choline positron emission tomography for the evaluation after treatment of localized prostate cancer. Eur Urol 2003;44:32–38; discussion 38–39. [CrossRef][Medline]
97. Picchio M, Messa C, Landoni C, et al. Value of [11C]choline-positron emission tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucose-positron emission tomography. J Urol 2003;169:1337–1340. [CrossRef][Medline]
98. de Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJ. Preoperative staging of pelvic lymph nodes in prostate cancer by 11C-choline PET. J Nucl Med 2003;44:331–335. [Abstract/Free Full Text]
99. Hara T, Kosaka N, Kishi H. PET imaging of prostate cancer using carbon-11-choline. J Nucl Med 1998;39:990–995. [Abstract/Free Full Text]
100. Hara T, Kosaka N, Kishi H. Development of (18)F-fluoroethylcholine for cancer imaging with PET: synthesis, biochemistry, and prostate cancer imaging. J Nucl Med 2002;43:187–199. [Abstract/Free Full Text]
101. Price DT, Coleman RE, Liao RP, Robertson CN, Polascik TJ, DeGrado TR. Comparison of [18 F]fluorocholine and [18 F]fluorodeoxyglucose for positron emission tomography of androgen dependent and androgen independent prostate cancer. J Urol 2002;168:273–280. [CrossRef][Medline]
102. Kwee SA, Coel MN, Lim J, Ko JP. Prostate cancer localization with 18fluorine fluorocholine positron emission tomography. J Urol 2005;173:252–255. [CrossRef][Medline]
103. Purohit RS, Shinohara K, Meng MV, Carroll PR. Imaging clinically localized prostate cancer. Urol Clin North Am 2003;30:279–293. [CrossRef][Medline]
104. Coakley FV, Qayyum A, Kurhanewicz J. Magnetic resonance imaging and spectroscopic imaging of prostate cancer. J Urol 2003;170(6 pt 2):S69–S75; discussion S75–S76. [CrossRef][Medline]
105. Swindle P, McCredie S, Russell P, et al. Pathologic characterization of human prostate tissue with proton MR spectroscopy. Radiology 2003;228:144–151. [Abstract/Free Full Text]
106. Engelbrecht MR, Jager GJ, Laheij RJ, Verbeek AL, van Lier HJ, Barentsz JO. Local staging of prostate cancer using magnetic resonance imaging: a meta-analysis. Eur Radiol 2002;12:2294–2302. [Medline]
107. Ackerstaff E, Pflug BR, Nelson JB, Bhujwalla ZM. Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prostatic epithelial cells. Cancer Res 2001;61:3599–3603. [Abstract/Free Full Text]
108. Coakley FV, Kurhanewicz J, Lu Y, et al. Prostate cancer tumor volume: measurement with endorectal MR and MR spectroscopic imaging. Radiology 2002;223:91–97. [Abstract/Free Full Text]
109. Yue K, Marumoto A, Binesh N, Thomas MA. 2D JPRESS of human prostates using an endorectal receiver coil. Magn Reson Med 2002;47:1059–1064. [CrossRef][Medline]
110. Swanson MG, Vigneron DB, Tran TK, Sailasuta N, Hurd RE, Kurhanewicz J. Single-voxel oversampled J-resolved spectroscopy of in vivo human prostate tissue. Magn Reson Med 2001;45:973–980. [CrossRef][Medline]
111. Swanson MG, Vigneron DB, Tabatabai ZL, et al. Proton HR-MAS spectroscopy and quantitative pathologic analysis of MRI/3D-MRSI-targeted postsurgical prostate tissues. Magn Reson Med 2003;50:944–954. [CrossRef][Medline]
112. Schricker AA, Pauly JM, Kurhanewicz J, Swanson MG, Vigneron DB. Dualband spectral-spatial RF pulses for prostate MR spectroscopic imaging. Magn Reson Med 2001;46:1079–1087. [CrossRef][Medline]
113. Kaji Y, Wada A, Imaoka I, et al. Proton two-dimensional chemical shift imaging for evaluation of prostate cancer: external surface coil vs. endorectal surface coil. J Magn Reson Imaging 2002;16:697–706.
114. Kim HW, Buckley DL, Peterson DM, et al. In vivo prostate magnetic resonance imaging and magnetic resonance spectroscopy at 3 Tesla using a transceive pelvic phased array coil: preliminary results. Invest Radiol 2003;38:443–451. [CrossRef][Medline]
115. Menard C, Smith IC, Somorjai RL, et al. Magnetic resonance spectroscopy of the malignant prostate gland after radiotherapy: a histopathologic study of diagnostic validity. Int J Radiat Oncol Biol Phys 2001;50:317–323. [CrossRef][Medline]
116. DiBiase SJ, Hosseinzadeh K, Gullapalli RP, et al. Magnetic resonance spectroscopic imaging-guided brachytherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2002;52:429–438. [CrossRef][Medline]
117. Mueller-Lisse UG, Vigneron DB, Hricak H, et al. Localized prostate cancer: effect of hormone deprivation therapy measured by using combined three-dimensional 1H MR spectroscopy and MR imaging—clinicopathologic case-controlled study. Radiology 2001;221:380–390. [Abstract/Free Full Text]
118. Mueller-Lisse UG, Swanson MG, Vigneron DB, et al. Time-dependent effects of hormone-deprivation therapy on prostate metabolism as detected by combined magnetic resonance imaging and 3D magnetic resonance spectroscopic imaging. Magn Reson Med 2001;46:49–57. [CrossRef][Medline]
119. Kurhanewicz J, Swanson MG, Wood PJ, Vigneron DB. Magnetic resonance imaging and spectroscopic imaging: improved patient selection and potential for metabolic intermediate endpoints in prostate cancer chemoprevention trials. Urology 2001;57:124–128. [Medline]
120. Zakian KL, Eberhardt S, Hricak H, et al. Transition zone prostate cancer: metabolic characteristics at 1H MR spectroscopic imaging—initial results. Radiology 2003;229:241–247. [Abstract/Free Full Text]
121. Harisinghani MG, Barentsz J, Hahn PF, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003;348:2491–2499. [Abstract/Free Full Text]
122. Daldrup-Link HE, Kaiser A, Helbich T, et al. Macromolecular contrast medium (feruglose) versus small molecular contrast medium (gadopentetate) enhanced magnetic resonance imaging: differentiation of benign and malignant breast lesions. Acad Radiol 2003;10:1237–1246. [CrossRef][Medline]
123. Rosenthal SA, Haseman MK, Polascik TJ. Utility of capromab pendetide (ProstaScint) imaging in the management of prostate cancer. Tech Urol 2001;7:27–37. [Medline]
124. Bander NH, Trabulsi EJ, Kostakoglu L, et al. Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen. J Urol 2003;170:1717–1721. [CrossRef][Medline]
125. Sandherr M, von Schilling C, Link T, et al. Pitfalls in imaging Hodgkin's disease with computed tomography and positron emission tomography using fluorine-18-fluorodeoxyglucose. Ann Oncol 2001;12:719–722. [Abstract/Free Full Text]
126. Rodriguez M, Rehn S, Ahlstrom H, Sundstrom C, Glimelius B. Predicting malignancy grade with PET in non-Hodgkin's lymphoma. J Nucl Med 1995;36:1790–1796. [Abstract/Free Full Text]
127. Jerusalem G, Beguin Y, Najjar F, et al. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-Hodgkin's lymphoma (NHL). Ann Oncol 2001;12:825–830. [Abstract/Free Full Text]
128. Hoffmann M, Kletter K, Diemling M, et al. Positron emission tomography with fluorine-18-2-fluoro-2-deoxy-D-glucose (F18-FDG) does not visualize extranodal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type. Ann Oncol 1999;10:1185–1189. [Abstract/Free Full Text]
129. Stumpe KD, Urbinelli M, Steinert HC, Glanzmann C, Buck A, von Schulthess GK. Whole-body positron emission tomography using fluorodeoxyglucose for staging of lymphoma: effectiveness and comparison with computed tomography. Eur J Nucl Med 1998;25:721–728. [CrossRef][Medline]
130. Moog F, Bangerter M, Diederichs CG, et al. Lymphoma: role of whole-body 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET in nodal staging. Radiology 1997;203:795–800. [Abstract/Free Full Text]
131. Kostakoglu L, Leonard JP, Kuji I, Coleman M, Vallabhajosula S, Goldsmith SJ. Comparison of fluorine-18 fluorodeoxyglucose positron emission tomography and Ga-67 scintigraphy in evaluation of lymphoma. Cancer 2002;94:879–888. [CrossRef][Medline]
132. Filmont JE, Vranjesevic D, Quon A, et al. Conventional imaging and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography for predicting the clinical outcome of previously treated non-Hodgkin's lymphoma patients. Mol Imaging Biol 2003;5:232–239. [CrossRef][Medline]
133. Cremerius U, Fabry U, Kroll U, et al. Clinical value of FDG PET for therapy monitoring of malignant lymphoma: results of a retrospective study in 72 patients. Nuklearmedizin 1999;38:24–30. [Medline]
134. Griffiths JR, Tate AR, Howe FA, Stubbs M. Magnetic resonance spectroscopy of cancer: practicalities of multi-centre trials and early results in non-Hodgkin's lymphoma. Eur J Cancer 2002;38:2085–2093. [CrossRef][Medline]
135. McMillan JH, Levine E, Stephens RH. Computed tomography in the evaluation of metastatic adenocarcinoma from an unknown primary site: a retrospective study. Radiology 1982;143:143–146. [Abstract/Free Full Text]
136. Scott CL, Kubaba I, Stewart JM, Hicks RJ, Rischin D. The utility of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography in the investigation of patients with disseminated carcinoma of unknown primary origin. Mol Imaging Biol 2005;7(3):236–243.[CrossRef][Medline]
137. Lonneux M, Reffad A. Metastases from unknown primary tumor: PET-FDG as initial diagnostic procedure? Clin Positron Imaging 2000;3:137–141. [CrossRef][Medline]
138. Bohuslavizki KH, Klutmann S, Kroger S, et al. FDG PET detection of unknown primary tumors. J Nucl Med 2000;41:816–822. [Abstract/Free Full Text]
139. Lassen U, Daugaard G, Eigtved A, Damgaard K, Friberg L. 18F-FDG whole body positron emission tomography (PET) in patients with unknown primary tumours (UPT). Eur J Cancer 1999;35:1076–1082. [CrossRef][Medline]
140. Dale PS, Foshag LJ, Wanek LA, Morton DL. Metastasis of primary melanoma to two separate lymph node basins: prognostic significance. Ann Surg Oncol 1997;4:13–18. [Abstract]
141. Klein M, Freedman N, Lotem M, et al. Contribution of whole body F-18-FDG-PET and lymphoscintigraphy to the assessment of regional and distant metastases in cutaneous malignant melanoma: a pilot study. Nuklearmedizin 2000;39:56–61. [Medline]
142. Wagner JD, Schauwecker D, Davidson D, et al. Inefficacy of F-18 fluorodeoxy-D-glucose-positron emission tomography scans for initial evaluation in early-stage cutaneous melanoma. Cancer 2005;104(3):570–579. [CrossRef][Medline]
143. Wagner JD, Schauwecker D, Davidson D, et al. Prospective study of fluorodeoxyglucose-positron emission tomography imaging of lymph node basins in melanoma patients undergoing sentinel node biopsy. J Clin Oncol 1999;17:1508–1515. [Abstract/Free Full Text]
144. Wagner JD, Schauwecker DS, Davidson D, Wenck S, Jung SH, Hutchins G. FDG-PET sensitivity for melanoma lymph node metastases is dependent on tumor volume. J Surg Oncol 2001;77:237–242. [CrossRef][Medline]
145. Schwimmer J, Essner R, Patel A, et al. A review of the literature for whole-body FDG PET in the management of patients with melanoma. Q J Nucl Med 2000;44:153–167. [Medline]
146. Finkelstein SE, Carrasquillo JA, Hoffman JM, et al. A prospective analysis of positron emission tomography and conventional imaging for detection of stage IV metastatic melanoma in patients undergoing metastasectomy. Ann Surg Oncol 2004;11(8):731–738. [Abstract/Free Full Text]
147. Sigg MB, Steinert H, Gratz K, Hugenin P, Stoeckli S, Klaus E. Staging head and neck tumors: [18F]fluorodeoxyglucose positron emission tomography compared with physical examination and conventional imaging modalities. J Oral Maxillofac Surg 2003;61:1022–1029. [CrossRef][Medline]
148. Nowak B, Di Martino E, Janicke S, et al. Diagnostic evaluation of malignant head and neck cancer by F-18-FDG PET compared to CT/MRI. Nuklearmedizin 1999;38:312–318. [Medline]
149. Schoder H, Yeung HW, Gonen M, Kraus D, Larson SM. Head and neck cancer: clinical usefulness and accuracy of PET/CT image fusion. Radiology 2004;231:65–72. [Abstract/Free Full Text]
150. Branstetter BF, Blodgett TM, Zimmer LA, et al. Head and neck malignancy: is PET/CT more accurate than PET or CT alone? Radiology 2005;235:580–586.
151. Anzai Y, Piccoli CW, Outwater EK, et al. Evaluation of neck and body metastases to nodes with ferumoxtran 10-enhanced MR imaging: phase III safety and efficacy study. Radiology 2003;228:777–788. [Abstract/Free Full Text]
152. Sigal R, Vogl T, Casselman J, et al. Lymph node metastases from head and neck squamous cell carcinoma: MR imaging with ultrasmall superparamagnetic iron oxide particles (Sinerem MR)—results of a phase-III multicenter clinical trial. Eur Radiol 2002;12:1104–1113. [CrossRef][Medline]
153. Mack MG, Balzer JO, Straub R, Eichler K, Vogl TJ. Superparamagnetic iron oxide-enhanced MR imaging of head and neck lymph nodes. Radiology 2002;222:239–244. [Abstract/Free Full Text]
154. Hoffman HT, Quets J, Toshiaki T, et al. Functional magnetic resonance imaging using iron oxide particles in characterizing head and neck adenopathy. Laryngoscope 2000;110:1425–1430. [CrossRef][Medline]
155. Anzai Y, Blackwell KE, Hirschowitz SL, et al. Initial clinical experience with dextran-coated superparamagnetic iron oxide for detection of lymph node metastases in patients with head and neck cancer. Radiology 1994;192:709–715. [Abstract/Free Full Text]
156. Greven KM, Williams DW 3rd, McGuirt WF Sr, et al. Serial positron emission tomography scans following radiation therapy of patients with head and neck cancer. Head Neck 2001;23:942–946. [CrossRef][Medline]
157. Jereczek-Fossa BA, Jassem J, Orecchia R. Cervical lymph node metastases of squamous cell carcinoma from an unknown primary. Cancer Treat Rev 2004;30:153–164. [CrossRef][Medline]
158. Wong WL, Saunders M. The impact of FDG PET on the management of occult primary head and neck tumours. Clin Oncol (R Coll Radiol) 2003;15:461–466. [Medline]
159. Fogarty GB, Peters LJ, Stewart J, Scott C, Rischin D, Hicks RJ. The usefulness of fluorine 18-labelled deoxyglucose positron emission tomography in the investigation of patients with cervical lymphadenopathy from an unknown primary tumor. Head Neck 2003;25:138–145. [CrossRef][Medline]
160. Regelink G, Brouwer J, de Bree R, et al. Detection of unknown primary tumours and distant metastases in patients with cervical metastases: value of FDG-PET versus conventional modalities. Eur J Nucl Med Mol Imaging 2002;29:1024–1030. [CrossRef][Medline]
161. Jungehulsing M, Scheidhauer K, Damm M, et al. 2[F]-fluoro-2-deoxy-D-glucose positron emission tomography is a sensitive tool for the detection of occult primary cancer (carcinoma of unknown primary syndrome) with head and neck lymph node manifestation. Otolaryngol Head Neck Surg 2000;123:294–301. [CrossRef][Medline]
162. Greven KM, Keyes JW Jr, Williams DW 3rd, McGuirt WF, Joyce WT 3rd. Occult primary tumors of the head and neck: lack of benefit from positron emission tomography imaging with 2-[F-18]fluoro-2-deoxy-D-glucose. Cancer 1999;86:114–118. [CrossRef][Medline]
163. Kresnik E, Mikosch P, Gallowitsch HJ, et al. Evaluation of head and neck cancer with 18F-FDG PET: a comparison with conventional methods. Eur J Nucl Med 2001;28:816–821. [CrossRef][Medline]
164. Lerut T, Flamen P, Ectors N, et al. Histopathologic validation of lymph node staging with FDG-PET scan in cancer of the esophagus and gastroesophageal junction: a prospective study based on primary surgery with extensive lymphadenectomy. Ann Surg 2000;232:743–752. [Medline]
165. Kole AC, Plukker JT, Nieweg OE, Vaalburg W. Positron emission tomography for staging of oesophageal and gastroesophageal malignancy. Br J Cancer 1998;78:521–527. [Medline]
166. Blackstock AW, Farmer MR, Lovato J, et al. A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer. Int J Radiat Oncol Biol Phys 2006;64(2):455–460. [CrossRef][Medline]
167. Levine EA, Farmer MR, Clark P, et al. Predictive value of 18-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer. Ann Surg 2006;243:472–478. [CrossRef][Medline]
168. Swisher SG, Erasmus J, Maish M, et al. 2-fluoro-2-deoxy-d-glucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma. Cancer 2004;101:1776–1785. [CrossRef][Medline]
169. Wieder HA, Brucher BL, Zimmermann F, et al. Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. J Clin Oncol 2004;22:900–908. [Abstract/Free Full Text]
170. Weber WA, Ott K, Becker K, et al. Prediction of response to preoperative chemotherapy in adenocarcinoma of the esophogastric junction by metabolic imaging. J Clin Oncol 2001;19:3058–3065. [Abstract/Free Full Text]
171. Frilling A, Tecklenborg K, Gorges R, Weber F, Clausen M, Broelsch EC. Preoperative diagnostic value of [(18)F] fluorodeoxyglucose positron emission tomography in patients with radioiodine-negative recurrent well-differentiated thyroid carcinoma. Ann Surg 2001;234:804–811. [CrossRef][Medline]
172. Stokkel MP, Duchateau CSJ, Dragoiescu C. The value of FDG-PET in the followup of differentiated thyroid cancer: a review of the literature. Q J Nucl Med Mol Imaging 2006;50(1):78–87.[Medline]
173. Palmedo H, Bucerius J, Joe A, et al. Integrated PET/CT in differentiated thyroid cancer: diagnostic accuracy and impact on patient management. J Nucl Med 2006;47(4):616–624.[Abstract/Free Full Text]
174. Kim S, Chung JK, Kang SB, et al. [18F]FDG PET as a substitute for second-look laparotomy in patients with advanced ovarian carcinoma. Eur J Nucl Med Mol Imaging 2004;31(2):196–201. [CrossRef][Medline]
175. Yoshida Y, Kurokawa T, Kawahara K, et al. Incremental benefits of FDG positron emission tomography over CT alone for the preoperative staging of ovarian cancer. AJR Am J Roentgenol 2004;182:227–233. [Abstract/Free Full Text]
176. Torizuka T, Nobezawa S, Kanno T, et al. Ovarian cancer recurrence: role of whole-body positron emission tomography using 2-[fluorine-18]-fluoro-2-deoxy-D-glucose. Eur J Nucl Med Mol Imaging 2002;29:797–803. [CrossRef][Medline]
177. Kawahara K, Yoshida Y, Kurokawa T, et al. Evaluation of positron emission tomography with tracer 18-fluorodeoxyglucose in addition to magnetic resonance imaging in the diagnosis of ovarian cancer in selected women after ultrasonography. J Comput Assist Tomogr 2004;28:505–516. [CrossRef][Medline]
178. Pannu HK, Cohade C, Bristow RE, Fishman EK, Wahl RL. PET-CT detection of abdominal recurrence of ovarian cancer: radiologic-surgical correlation. Abdom Imaging 2004;29:398–403. [Medline]
179. Drieskens O, Stroobants S, Gysen M, Vandenbosch G, Mortelmans L, Vergote I. Positron emission tomography with FDG in the detection of peritoneal and retroperitoneal metastases of ovarian cancer. Gynecol Obstet Invest 2003;55:130–134. [CrossRef][Medline]
180. Cho SM, Ha HK, Byun JY, Lee JM, Kim CJ, Nam-Koong SE. Usefulness of FDG PET for assessment of early recurrent epithelial ovarian cancer. AJR Am J Roentgenol 2002;179:391–395. [Abstract/Free Full Text]
181. Murakami M, Miyamoto T, Iida T, et al. Whole-body positron emission tomography and tumor marker CA 125 for prediction of recurrence in epithelial ovarian cancer. Int J Gynecol Cancer 2006;16(suppl 1):99–107.[CrossRef][Medline]
182. Takekuma M, Maeda M, Ozawa T, Yasumi K, Torizuka T. Positron emission tomography with 18F-fluoro-2-deoxyglucose for the detection of recurrent ovarian cancer. Int J Clin Oncol 2005;10(3):177–181.[CrossRef][Medline]
183. Nanni C, Rubello D, Farsad M, et al. (18)F-FDG PET/CT in the evaluation of recurrent ovarian cancer: a prospective study on forty-one patients. Eur J Surg Oncol 2005;31(7):792–797.[CrossRef][Medline]
184. Subhas N, Patel PV, Pannu HK, Jacene HA, Fishman EK, Wahl RL. Imaging of pelvic malignancies with in-line FDG PET-CT: case examples and common pitfalls of FDG-PET. RadioGraphics 2005;25(4):1031–1043.[Abstract/Free Full Text]
185. Avril N, Sassen S, Schmalfeldt B, et al. Prediction of response to neoadjuvant chemotherapy by sequential F-18-fluorodeoxyglucose positron emission tomography in patients with advanced-stage ovarian cancer. J Clin Oncol 2005;23(30):7445–7453. [Abstract/Free Full Text]
186. Spermon JR, De Geus-Oei LF, Kiemeney LA, Witjes JA, Oyen WJ. The role of (18)fluoro-2-deoxyglucose positron emission tomography in initial staging and re-staging after chemotherapy for testicular germ cell tumours. BJU Int 2002;89:549–556. [CrossRef][Medline]
187. Hain SF, O'Doherty MJ, Timothy AR, Leslie MD, Partridge SE, Huddart RA. Fluorodeoxyglucose PET in the initial staging of germ cell tumours. Eur J Nucl Med 2000;27:590–594. [CrossRef][Medline]
188. Cremerius U, Wildberger JE, Borchers H, et al. Does positron emission tomography using 18-fluoro-2-deoxyglucose improve clinical staging of testicular cancer? results of a study in 50 patients. Urology 1999;54:900–904. [CrossRef][Medline]
189. Lassen U, Daugaard G, Eigtved A, Hojgaard L, Damgaard K, Rorth M. Whole-body FDG-PET in patients with stage I non-seminomatous germ cell tumours. Eur J Nucl Med Mol Imaging 2003;30:396–402. [Medline]
190. Sanchez D, Zudaire JJ, Fernandez JM, et al. 18F-fluoro-2-deoxyglucose-positron emission tomography in the evaluation of nonseminomatous germ cell tumours at relapse. BJU Int 2002;89:912–916. [CrossRef][Medline]
191. Hain SF, O'Doherty MJ, Timothy AR, Leslie MD, Harper PG, Huddart RA. Fluorodeoxyglucose positron emission tomography in the evaluation of germ cell tumours at relapse. Br J Cancer 2000;83:863–869. [CrossRef][Medline]
192. De Santis M, Becherer A, Bokemeyer C, et al. 2-18fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial. J Clin Oncol 2004;22:1034–1039.[Abstract/Free Full Text]
193. Becherer A, DeSantis M, Karanikas G, et al. FDG PET is superior to CT in the prediction of viable tumour in post-chemotherapy seminoma residuals. Eur J Radiol 2005;54(2):284–288. [CrossRef][Medline]
194. Bokemeyer C, Kollmannsberger C, Oechsle K, et al. Early prediction of treatment response to high-dose salvage chemotherapy in patients with relapsed germ cell cancer using [18F]FDG PET. Br J Cancer 2002;86:506–511. [CrossRef][Medline]
195. Karapetis CS, Strickland AH, Yip D, van der Walt JD, Harper PG. PET and PLAP in suspected testicular cancer relapse: beware sarcoidosis. Ann Oncol 2001;12:1485–1488. [Abstract/Free Full Text]
196. Muggia FM, Conti PS. Seminoma and sarcoidosis: a cause for false positive mediastinal uptake in PET? Ann Oncol 1998;9:924.[Free Full Text]
197. Kumar R, Chauhan A, Lakhani P, Xiu Y, Zhuang H, Alavi A. 2-Deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography in characterization of solid renal masses. Mol Imaging Biol 2005;7(60):431–439.[CrossRef][Medline]
198. Aide N, Cappele O, Bottet P, et al. Efficiency of [(18)F]FDG PET in characterising renal cancer and detecting distant metastases: a comparison with CT. Eur J Nucl Med Mol Imaging 2003;30(9):1236–1245. [CrossRef][Medline]
199. Safaei A, Figlin R, Hoh CK, et al. The usefulness of F-18 deoxyglucose whole-body positron emission tomography (PET) for re-staging of renal cell cancer. Clin Nephrol 2002;57:56–62. [Medline]
200. Jadvar H, Kherbache HM, Pinski JK, Conti PS. Diagnostic role of [F-18]-FDG positron emission tomography in restaging renal cell carcinoma. Clin Nephrol 2003;60:395–400. [Medline]
201. Kang DE, White RL Jr, Zuger JH, Sasser HC, Teigland CM. Clinical use of fluorodeoxyglucose F 18 positron emission tomography for detection of renal cell carcinoma. J Urol 2004;171:1806–1809. [CrossRef][Medline]
202. Majhail NS, Urbain JL, Albani JM, et al. F-18 fluorodeoxyglucose positron emission tomography in the evaluation of distant metastases from renal cell carcinoma. J Clin Oncol 2003;21:3995–4000. [Abstract/Free Full Text]
203. Szabo Z, Xia J, Mathews WB, Brown PR. Future direction of renal positron emission tomography. Semin Nucl Med 2006;36(1):36–50. [CrossRef][Medline]
204. Hofer C, Kubler H, Hartung R, Breul J, Avril N. Diagnosis and monitoring of urological tumors using positron emission tomography. Eur Urol 2001;40:481–487. [Medline]
205. Kosuda S, Kison PV, Greenough R, Grossman HB, Wahl RL. Preliminary assessment of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with bladder cancer. Eur J Nucl Med 1997;24:615–620. [Medline]
206. de Jong IJ, Pruim J, Elsinga PH, Jongen MM, Mensink HJ, Vaalburg W. Visualisation of bladder cancer using (11)C-choline PET: first clinical experience. Eur J Nucl Med Mol Imaging 2002;29:1283–1288. [CrossRef][Medline]
207. Narayan K, McKenzie AF, Hicks RJ, Fisher R, Bernshaw D, Bau S. Relation between FIGO stage, primary tumor volume, and presence of lymph node metastases in cervical cancer patients referred for radiotherapy. Int J Gynecol Cancer 2003;13:657–663. [CrossRef][Medline]
208. Unger JB, Ivy JJ, Connor P, et al. Detection of recurrent cervical cancer by whole-body FDG PET scan in asymptomatic and symptomatic women. Gynecol Oncol 2004;94:212–216. [CrossRef][Medline]
209. Chang TC, Law KS, Hong JH, et al. Positron emission tomography for unexplained elevation of serum squamous cell carcinoma antigen levels during follow-up for patients with cervical malignancies: a phase II study. Cancer 2004;101:164–171. [CrossRef][Medline]
210. Wong TZ, Jones EL, Coleman RE. Positron emission tomography with 2-deoxy-2-[(18)F]fluoro-D-glucose for evaluating local and distant disease in patients with cervical cancer. Mol Imaging Biol 2004;6:55–62. [CrossRef][Medline]
211. Ryu SY, Kim MH, Choi SC, Choi CW, Lee KH. Detection of early recurrence with 18F-FDG PET in patients with cervical cancer. J Nucl Med 2003;44:347–352. [Abstract/Free Full Text]
212. Rose PG, Adler LP, Rodriguez M, Faulhaber PF, Abdul-Karim FW, Miraldi F. Positron emission tomography for evaluating para-aortic nodal metastasis in locally advanced cervical cancer before surgical staging: a surgicopathologic study. J Clin Oncol 1999;17:41–45. [Abstract/Free Full Text]
213. Nakamoto Y, Eisbruch A, Achtyes ED, et al. Prognostic value of positron emission tomography using F-18-fluorodeoxyglucose in patients with cervical cancer undergoing radiotherapy. Gynecol Oncol 2002;84:289–295. [CrossRef][Medline]
214. Wright JD, Dehdashti F, Herzog TJ, et al. Preoperative lymph node staging of early-stage cervical carcinoma by [18F]-fluoro-2-deoxy-D-glucose-positron emission tomography. Cancer 2005;104(11):2484–2491. [CrossRef][Medline]
215. Lai CH, Huang KG, See LC, et al. Restaging of recurrent cervical carcinoma with dual-phase [18F]fluoro-2-deoxy-D-glucose positron emission tomography. Cancer 2004;100:544–552. [CrossRef][Medline]
216. Tsai CS, Chang TC, Lai CH, et al. Preliminary report of using FDG-PET to detect extrapelvic lesions in cervical cancer patients with enlarged pelvic lymph nodes on MRI/CT. Int J Radiat Oncol Biol Phys 2004;58:1506–1512. [CrossRef][Medline]
217. Grigsby PW, Siegel BA, Dehdashti F, Rader J, Zoberi I. Posttherapy [18F] fluorodeoxyglucose positron emission tomography in carcinoma of the cervix: response and outcome. J Clin Oncol 2004;22:2167–2171. [Abstract/Free Full Text]
218. Narayan K, Hicks RJ, Jobling T, Bernshaw D, McKenzie AF. A comparison of MRI and PET scanning in surgically staged loco-regionally advanced cervical cancer: potential impact on treatment. Int J Gynecol Cancer 2001;11:263–271. [CrossRef][Medline]
219. Mertz HR, Sechopoulos P, Delbeke D, Leach SD. EUS, PET, and CT scanning for evaluation of pancreatic adenocarcinoma. Gastrointest Endosc 2000;52:367–371. [CrossRef][Medline]
220. Delbeke D, Rose DM, Chapman WC, et al. Optimal interpretation of FDG PET in the diagnosis, staging and management of pancreatic carcinoma. J Nucl Med 1999;40:1784–1791. [Abstract/Free Full Text]
221. Rose DM, Delbeke D, Beauchamp RD, et al. 18Fluorodeoxyglucose-positron emission tomography in the management of patients with suspected pancreatic cancer. Ann Surg 1999;229:729–737; discussion 737–738. [CrossRef][Medline]
222. Keogan MT, Tyler D, Clark L, et al. Diagnosis of pancreatic carcinoma: role of FDG PET. AJR Am J Roentgenol 1998;171:1565–1570. [Abstract/Free Full Text]
223. Heinrich S, Goerres GW, Schafer M, et al. Positron emission tomography/computed tomography influences on the management of resectable pancreatic cancer and its cost-effectiveness. Ann Surg 2005;242(2):235–243. [CrossRef][Medline]
224. Saisho H, Yamaguchi T. Diagnostic imaging for pancreatic cancer: computed tomography, magnetic resonance imaging, and positron emission tomography. Pancreas 2004;28:273–278. [CrossRef][Medline]
225. Jadvar H, Fischman AJ. Evaluation of pancreatic carcinoma with FDG PET. Abdom Imaging 2001;26:254–259. [CrossRef][Medline]
226. Maisey NR, Webb A, Flux GD, et al. FDG-PET in the prediction of survival of patients with cancer of the pancreas: a pilot study. Br J Cancer 2000;83:287–293. [CrossRef][Medline]
227. Sperti C, Pasquali C, Chierichetti F, Ferronato A, Decet G, Pedrazzoli S. 18-Fluorodeoxyglucose positron emission tomography in predicting survival of patients with pancreatic carcinoma. J Gastrointest Surg 2003;7:953–959; discussion 959–960. [CrossRef][Medline]
228. Nakata B, Nishimura S, Ishikawa T, et al. Prognostic predictive value of 18F-fluorodeoxyglucose positron emission tomography for patients with pancreatic cancer. Int J Oncol 2001;19:53–58. [Medline]
229. Nakata B, Chung YS, Nishimura S, et al. 18F-fluorodeoxyglucose positron emission tomography and the prognosis of patients with pancreatic adenocarcinoma. Cancer 1997;79:695–699. [CrossRef][Medline]
230. Zimny M, Bares R, Fass J, et al. Fluorine-18 fluorodeoxyglucose positron emission tomography in the differential diagnosis of pancreatic carcinoma: a report of 106 cases. Eur J Nucl Med 1997;24:678–682. [Medline]
231. Stollfuss JC, Glatting G, Friess H, Kocher F, Berger HG, Reske SN. 2-(fluorine-18)-fluoro-2-deoxy-D-glucose PET in detection of pancreatic cancer: value of quantitative image interpretation. Radiology 1995;195:339–344. [Abstract/Free Full Text]
232. van Kouwen MC, Jansen JB, van Goor H, de Castro S, Oyen WJ, Drenth JP. FDG-PET is able to detect pancreatic carcinoma in chronic pancreatitis. Eur J Nucl Med Mol Imaging 2005;32(4):399–404.[CrossRef][Medline]
233. Ruf J, Lopez Hanninen E, Oettle H, et al. Detection of recurrent pancreatic cancer: comparison of FDG-PET PET with CT/MRI. Pancreatology 2005;5(2-3):266–272. [CrossRef][Medline]
234. Bradley JD, Dehdashti F, Mintun MA, Govindan R, Trinkaus K, Siegel BA. Positron emission tomography in limited-stage small-cell lung cancer: a prospective study. J Clin Oncol 2004;22:3248–3254. [Abstract/Free Full Text]
235. Blum R, MacManus MP, Rischin D, Michael M, Ball D, Hicks RJ. Impact of positron emission tomography on the management of patients with small-cell lung cancer: preliminary experience. Am J Clin Oncol 2004;27:164–171. [CrossRef][Medline]
236. Kamel EM, Zwahlen D, Wyss MT, Stumpe KD, von Schulthess GK, Steinert HC. Whole-body (18)F-FDG PET improves the management of patients with small cell lung cancer. J Nucl Med 2003;44:1911–1917. [Abstract/Free Full Text]
237. Zhao DS, Valdivia AY, Li Y, Blaufox MD. 18F-fluorodeoxyglucose positron emission tomography in small-cell lung cancer. Semin Nucl Med 2002;32:272–275. [CrossRef][Medline]
238. Shen YY, Shiau YC, Wang JJ, Ho ST, Kao CH. Whole-body 18F-2-deoxyglucose positron emission tomography in primary staging small cell lung cancer. Anticancer Res 2002;22:1257–1264. [Medline]
239. Chin R Jr, McCain TW, Miller AA, et al. Whole body FDG-PET for the evaluation and staging of small cell lung cancer: a preliminary study. Lung Cancer 2002;37:1–6. [Medline]
240. Schumacher T, Brink I, Mix M, et al. FDG-PET imaging for the staging and follow-up of small cell lung cancer. Eur J Nucl Med 2001;28:483–488. [CrossRef][Medline]
241. Pandit N, Gonen M, Krug L, Larson SM. Prognostic value of [18F]FDG-PET imaging in small cell lung cancer. Eur J Nucl Med Mol Imaging 2003;30:78–84. [CrossRef][Medline]
242. Crotty E, Patz EF Jr. FDG-PET imaging in patients with paraneoplastic syndromes and suspected small cell lung cancer. J Thorac Imaging 2001;16:89–93. [CrossRef][Medline]
243. Eriksson B, Bergstrom M, Sundin A, et al. The role of PET in localization of neuroendocrine and adrenocortical tumors. Ann N Y Acad Sci 2002;970:159–169. [Medline]
244. Sundin A, Eriksson B, Bergstrom M, Langstrom B, Oberg K, Orlefors H. PET in the diagnosis of neuroendocrine tumors. Ann N Y Acad Sci 2004;1014:246–257. [CrossRef][Medline]
245. Orlefors H, Sundin A, Ahlstrom H, et al. Positron emission tomography with 5-hydroxytryprophan in neuroendocrine tumors. J Clin Oncol 1998;16:2534–2541. [Abstract]
246. Anderson CJ, Dehdashti F, Cutler PD, et al. 64Cu-TETA-octreotide as a PET imaging agent for patients with neuroendocrine tumors. J Nucl Med 2001;42:213–221. [Abstract/Free Full Text]
247. Becherer A, Szabo M, Karanikas G, et al. Imaging of advanced neuroendocrine tumors with (18)F-FDOPA PET. J Nucl Med 2004;45:1161–1167. [Abstract/Free Full Text]
248. Jacob T, Grahek D, Younsi N, et al. Positron emission tomography with [(18)F]FDOPA and [(18)F]FDG in the imaging of small cell lung carcinoma: preliminary results. Eur J Nucl Med Mol Imaging 2003;30:1266–1269. [CrossRef][Medline]
249. Pasquali C, Rubello D, Sperti C, et al. Neuroendocrine tumor imaging: can 18F-fluorodeoxyglucose positron emission tomography detect tumors with poor prognosis and aggressive behavior? World J Surg 1998;22:588–592.
250. Wudel LJ Jr, Delbecke D, Morris D, et al. The role of [18F]fluorodeoxyglucose positron emission tomography imaging in the evaluation of hepatocellular carcinoma. Am Surg 2003;69(2):117–124. [Medline]
251. Ho CL, Yu SC, Yeung DW. 11C-acetate PET imaging in hepatocellular carcinoma and other liver masses. J Nucl Med 2003;44:213–221. [Abstract/Free Full Text]
252. Bohm B, Voth M, Geoghegan J, et al. Impact of positron emission tomography on strategy in liver resection for primary and secondary liver tumors. J Cancer Res Clin Oncol 2004;130(5):266–272. [CrossRef][Medline]
253. Lee JM, Kim IH, Kwak HS, Youk JH, Han YM, Kim CS. Detection of small hypervascular hepatocellular carcinomas in cirrhotic patients: comparison of superparamagnetic iron oxide-enhanced MR imaging with dual-phase spiral CT. Korean J Radiol 2003;4:1–8. [Medline]
254. Mori K, Yoshioka H, Itai Y, et al. Arterioportal shunts in cirrhotic patients: evaluation of the difference between tumorous and nontumorous arterioportal shunts on MR imaging with superparamagnetic iron oxide. AJR Am J Roentgenol 2000;175:1659–1664. [Abstract/Free Full Text]
255. Tanimoto A, Yuasa Y, Shinmoto H, et al. Superparamagnetic iron oxide-mediated hepatic signal intensity change in patients with and without cirrhosis: pulse sequence effects and Kupffer cell function. Radiology 2002;222:661–666. [Abstract/Free Full Text]
256. Elizondo G, Weissleder R, Stark DD, et al. Hepatic cirrhosis and hepatitis: MR imaging enhanced with superparamagnetic iron oxide. Radiology 1990;174:797–801. [Abstract/Free Full Text]
257. Corbin IR, Ryner LN, Singh H, Minuk GY. Quantitative hepatic phosphorus-31 magnetic resonance spectroscopy in compensated and decompensated cirrhosis. Am J Physiol Gastrointest Liver Physiol 2004;287:G379–G384. [Abstract/Free Full Text]
258. Menon DK, Sargentoni J, Taylor-Robinson SD, et al. Effect of functional grade and etiology on in vivo hepatic phosphorus-31 magnetic resonance spectroscopy in cirrhosis: biochemical basis of spectral appearances. Hepatology 1995;21:417–427. [CrossRef][Medline]
259. McCauley TR, Rifkin MD, Ledet CA. Pelvic lymph node visualization with MR imaging using local administration of ultra-small superparamagnetic iron oxide contrast. J Magn Reson Imaging 2002;15:492–497. [CrossRef][Medline]
260. Pannu HK, Wang KP, Borman TL, Bluemke DA. MR imaging of mediastinal lymph nodes: evaluation using a superparamagnetic contrast agent. J Magn Reson Imaging 2000;12:899–904. [CrossRef][Medline]
261. Nguyen BC, Stanford W, Thompson BH, et al. Multicenter clinical trial of ultrasmall superparamagnetic iron oxide in the evaluation of mediastinal lymph nodes in patients with primary lung carcinoma. J Magn Reson Imaging 1999;10:468–473. [CrossRef][Medline]
262. Bellin MF, Roy C, Kinkel K, et al. Lymph node metastases: safety and effectiveness of MR imaging with ultrasmall superparamagnetic iron oxide particles—initial clinical experience. Radiology 1998;207:799–808. [Abstract/Free Full Text]
263. Harisinghani MG, Saini S, Hahn PF, Weissleder R, Mueller PR. MR imaging of lymph nodes in patients with primary abdominal and pelvic malignancies using ultrasmall superparamagnetic iron oxide (Combidex). Acad Radiol 1998;5(suppl 1):S167–S169, discussion S183–S184. [CrossRef][Medline]
264. Weissleder R, Elizondo G, Wittenberg J, Rabito CA, Bengele HH, Josephson L. Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. Radiology 1990;175:489–493. [Abstract/Free Full Text]
265. Bakheet SM, Saleem M, Powe J, Al-Amro A, Larsson SG, Mahassin Z. F-18 fluorodeoxyglucose chest uptake in lung inflammation and infection. Clin Nucl Med 2000;25:273–278. [CrossRef][Medline]
266. Zhuang H, Yu JQ, Alavi A. Applications of fluorodeoxyglucose-PET imaging in the detection of infection and inflammation and other benign disorders. Radiol Clin North Am 2005;43(1):121–134. [CrossRef][Medline]
267. Love C, Tomas MB, Tronco GG, Palestro CJ. FDG PET of infection and inflammation. RadioGraphics 2005;25(5):1357–1368. [Abstract/Free Full Text]
268. Zhuang H, Alavi A. 18-fluorodeoxyglucose positron emission tomographic imaging in the detection and monitoring of infection and inflammation. Semin Nucl Med 2002;32:47–59. [CrossRef][Medline]
269. Bleeker-Rovers CP, de Kleijn EM, Corstens FH, van der Meer JW, Oyen WJ. Clinical value of FDG PET in patients with fever of unknown origin and patients suspected of focal infection or inflammation. Eur J Nucl Med Mol Imaging 2004;31:29–37. [CrossRef][Medline]
270. Buysschaert I, Vanderschueren S, Blockmans D, Mortelmans L, Knockaert D. Contribution of (18)fluoro-deoxyglucose positron emission tomography to the work-up of patients with fever of unknown origin. Eur J Intern Med 2004;15(3):151–156.[CrossRef][Medline]
271. van Waarde A, Cobben DC, Suurmeijer AJ, et al. Selectivity of 18F-FLT and 18F-FDG for differentiating tumor from inflammation in a rodent model. J Nucl Med 2004;45:695–700. [Abstract/Free Full Text]
272. Lewis PJ, Salama A. Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis. J Nucl Med 1994;35:1647–1649. [Abstract/Free Full Text]
273. Brudin LH, Valind SO, Rhodes CG, et al. Fluorine-18 deoxyglucose uptake in sarcoidosis measured with positron emission tomography. Eur J Nucl Med 1994;21:297–305. [CrossRef][Medline]
274. Botnar RM, Perez AS, Witte S, et al. In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent. Circulation 2004;109:2023–2029. [Abstract/Free Full Text]
275. Flacke S, Fischer S, Scott MJ, et al. Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques. Circulation 2001;104:1280–1285. [Abstract/Free Full Text]
276. Winter PM, Caruthers SD, Yu X, et al. Improved molecular imaging contrast agent for detection of human thrombus. Magn Reson Med 2003;50:411–416. [CrossRef][Medline]
277. Yu X, Song SK, Chen J, et al. High-resolution MRI characterization of human thrombus using a novel fibrin-targeted paramagnetic nanoparticle contrast agent. Magn Reson Med 2000;44:867–872. [CrossRef][Medline]
278. Woods M, Zhang S, Ebron VH, Sherry AD. pH-sensitive modulation of the second hydration sphere in lanthanide(III) tetraamide-DOTA complexes: a novel approach to smart MR contrast media. Chemistry 2003;9:4634–4640. [CrossRef][Medline]
279. Zhou J, Wilson DA, Sun PZ, Klaus JA, Van Zijl PC. Quantitative description of proton exchange processes between water and endogenous and exogenous agents for WEX, CEST, and APT experiments. Magn Reson Med 2004;51:945–952. [CrossRef][Medline]
280. Aime S, Delli Castelli D, Terreno E. Supramolecular adducts between poly-L-arginine and [TmIIIdotp]: a route to sensitivity-enhanced magnetic resonance imaging-chemical exchange saturation transfer agents. Angew Chem Int Ed Engl 2003;42:4527–4529. [CrossRef]
281. Bottomley PA, Ouwerkerk R, Lee RF, Weiss RG. Four-angle saturation transfer (FAST) method for measuring creatine kinase reaction rates in vivo. Magn Reson Med 2002;47:850–863. [CrossRef][Medline]
282. Ward KM, Balaban RS. Determination of pH using water protons and chemical exchange dependent saturation transfer (CEST). Magn Reson Med 2000;44:799–802. [CrossRef][Medline]
283. Chan KW, Barra S, Botta M, Wong WT. Novel gadolinium(III) polyaminocarboxylate macrocyclic complexes as potential magnetic resonance imaging contrast agents. J Inorg Biochem 2004;98:677–682. [CrossRef][Medline]
284. Lindner JR. Molecular imaging with contrast ultrasound and targeted microbubbles. J Nucl Cardiol 2004;11:215–221. [CrossRef][Medline]
285. Dayton PA, Ferrara KW. Targeted imaging using ultrasound. J Magn Reson Imaging 2002;16:362–377. [CrossRef][Medline]
286. Blasberg RG, Tjuvajev JG. Herpes simplex virus thymidine kinase as a marker/reporter gene for PET imaging of gene therapy. Q J Nucl Med 1999;43:163–169. [Medline]
287. Pantuck AJ, Berger F, Zisman A, et al. CL1-SR39: a noninvasive molecular imaging model of prostate cancer suicide gene therapy using positron emission tomography. J Urol 2002;168:1193–1198. [CrossRef][Medline]
288. Weber WA. Use of PET for monitoring cancer therapy and for predicting outcome. J Nucl Med 2005;46:983–995. [Abstract/Free Full Text]
289. Avril NE, Weber WA. Monitoring response to treatment in patients unilizing PET. Radiol Clin North Am 2005;43:189–204. [CrossRef][Medline]
290. Choi H, Charnsangavej C, de Castro Faria S, et al. CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol 2004;183:1619–1628. [Abstract/Free Full Text]
291. Antoch G, Kanja J, Bauer S, et al. Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors. J Nucl Med 2004;45:357–365. [Abstract/Free Full Text]
292. Gayed I, Vu T, Iyer R, et al. The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors. J Nucl Med 2004;45(1):17–21. [Published correction appears in J Nucl Med 2004;45(11):1803.] [Abstract/Free Full Text]
293. Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 2003;17:545–580. [Free Full Text]
294. Jaffer FA, Weissleder R. Molecular imaging in the clinical arena. JAMA 2005;293:855–862. [Abstract/Free Full Text]
295. Gambhir SS. Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer 2002;2(9):683–693. [CrossRef][Medline]
296. Kelloff GJ, Krohn KA, Larson SM, et al. The progress and promise of molecular imaging probes in oncologic drug development. Clin Cancer Res 2005;11(22):7967–7985. [Abstract/Free Full Text]

This Article Abstract Figures Only Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Margolis, D. J. A. Articles by Gambhir, S. S. Search for Related Content PubMed PubMed Citation Articles by Margolis, D. J. A. Articles by Gambhir, S. S.