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(Radiology. 1999;211:681-686.)
© RSNA, 1999

Nuclear Medicine

Pharmacokinetic Imaging of 11C Ethanol with PET in Eight Patients with Hepatocellular Carcinomas Who Were Scheduled for Treatment with Percutaneous Ethanol Injection1

Antonia Dimitrakopoulou-Strauss, MD, Ludwig G. Strauss, MD, Frank Gutzler, MD, PhD, Gisela Irngartinger, MD, George Kontaxakis, PhD, Duk Kyu Kim, MD, Franz Oberdorfer, PhD and Gerhard van Kaick, MD

1 From the Departments of Oncological Diagnostics and Therapy (A.D.S., L.G.S., G.I., G.K., G.v.K.) and Radiochemistry and Radiopharmacology (F.O.), Medical PET-Group, Biological Imaging, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; the Department of Internal Medicine IV, University of Heidelberg, Germany (F.G.); and the Department of Nuclear Medicine, Dong-A University, Pusan, South Korea (D.K.K.). From the 1997 RSNA scientific assembly. Received February 11, 1998; revision requested April 15; revision received September 21; accepted December 15. Address reprint requests to A.D.S.


   Abstract
TOP
 Abstract
Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To evaluate the carbon 11 ethanol kinetics with positron emission tomography after intratumoral injection of the tracer and assess its redistribution and dilution in patients who have hepatocellular carcinomas and who were scheduled for treatment with percutaneous ethanol injection.

MATERIALS AND METHODS: The study included eight patients with hepatocellular carcinomas. 11C ethanol was administered via a puncture needle positioned with ultrasonographic guidance. Parametric images based on the Fourier transformation were created for further analysis of the local distribution patterns of the tracer. The ratio of the 45-minute postinjection standardized uptake value to the 5-minute postinjection standardized uptake value was used for the evaluation of ethanol dilution.

RESULTS: Five of eight tumors demonstrated almost constant uptake values after the initial distribution phase. In contrast, a rapid elimination of the 11C ethanol from the tumor was documented in three of eight tumors. The 45 minute–to–5 minute ratio was 0.18–0.67 (median value, 0.56) in the tumors. The time-activity curves of the normal liver parenchyma increased slowly but steadily with time owing to a low ethanol elimination from the tumor. Fourier transformation demonstrated inhomogeneous parts on the amplitude images in seven of eight tumors and random redistribution on the phase images in six of eight tumors.

CONCLUSION: Inhomogeneous drug distribution and drug dilution in the target area are likely to be the major limiting parameters for therapy response.

Index terms: Alcohol, 761.12163 • Liver neoplasms, chemotherapeutic infusion, 761.12168, 761.323 • Liver neoplasms, radionuclide studies, 761.12163, 761.323 • Liver neoplasms, therapy, 761.12163, 761.323


   Introduction
TOP
 Abstract
 Introduction
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Percutaneous ethanol injection is used for curative or palliative treatment of hepatocellular carcinomas. Percutaneous ethanol injection is considered a reliable alternative to surgical resection for patients with cirrhosis and a single, small hepatocellular carcinoma (1). Major problems when using percutaneous ethanol injection are the assessment of the ethanol distribution in the target area and the noninvasive evaluation of early response. Morphologic imaging modalities, like ultrasonography, computed tomography (CT), or magnetic resonance (MR) imaging, have been used to determine the effect of percutaneous ethanol injection by using morphologic criteria, such as the size of the necrotic area of the lesion and the presence of peripheral nodularity. CT evidence of necrosis and lack of nodularity immediately after percutaneous ethanol injection were suggestive of absence of disease (2).

Nagel and Bernardino (3) examined the role of contrast material–enhanced and nonenhanced MR imaging in nine patients with histologically proved hepatocellular carcinomas and two liver metastases from colon carcinoma. These authors examined the patients prior to percutaneous ethanol injection and in a fourfold follow-up after percutaneous ethanol injection. They reported that the MR appearance of the lesions after percutaneous ethanol injection was variable and that the signal characteristics of most lesions did not change considerably over time. They concluded that the MR appearance of lesions treated by means of percutaneous ethanol injection is not a reliable indicator for residual tumor tissue.

Some authors (4,5) examined the role of 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomographic (PET) follow-up studies in tumors to assess therapy outcome after chemotherapeutic treatment. The authors (4,5) confirmed some limitations of the FDG follow-up studies, like the so-called flare phenomenon (temporary increase in FDG uptake shortly after chemotherapy) and the importance of the correct choice of a representative interval between the PET study and the last chemotherapeutic cycle to evaluate therapy response.

The limitations of both morphologic imaging modalities, like CT and MR imaging, as well as of functional imaging with FDG PET, direct one to the use of radiolabeled ethanol to gain more information about the kinetics of the drug in the target area. For this purpose, we used PET with carbon 11 ethanol and the same administration route as used for therapy. Previous PET pharmacokinetic studies (6–8) in which radiolabeled cytostatic agents, like 18F fluorouracil, were used in patients with liver metastases from colorectal carcinoma showed that PET with 18F fluorouracil was superior to PET with FDG because one study prior to onset of chemotherapy was predictive of therapy response.

The aims of this study were the evaluation of the kinetics of 11C ethanol after intratumoral injection of the tracer in the tumor area and the assessment of drug redistribution in patients who had hepatocellular carcinomas and who were scheduled for treatment with percutaneous ethanol injection. Furthermore, we evaluated the elimination and dilution of the ethanol and the time and spatial distribution patterns of the drug in the tumor area.


   MATERIALS AND METHODS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
The final analysis includes eight patients (seven men, one woman; age range, 52–78 years; mean age, 66 years) with unresectable hepatocellular carcinomas. All patients had been excluded from surgical resection and were scheduled for percutaneous ethanol injection with US guidance. Patients had liver cirrhosis graded as Child A due to alcoholism (n = 5), hepatitis C (n = 2), or hemochromatosis (n = 1). The tumors were histologically confirmed as hepatocellular carcinomas (International Union against Cancer Stage IIIA–IVA). In four patients, a well-differentiated tumor was documented at biopsy, while four other patients had hepatocellular carcinoma that was not as well differentiated. The number of lesions, with 3–6-cm diameters, varied from one to three for each patient. None of the patients had extrahepatic metastatic disease. The number of thrombocytes exceeded 50 x 103/µL (50 x 109/L). The Quick test value was higher than 50, and the Karnofsky scale value was above 60.

All patients included in the study were treated by the oncologist (F.G.). The treatment was repeated up to six times for each node by using a dedicated 22-gauge needle (Pflugbeil, Munich, Germany) with holes placed on each side and positioned under US guidance. Under sterile conditions and local anesthesia, 2–10 mL of nonlabeled ethanol (Alkohol-Konzentrat 95%; Braun, Melsungen, Germany) was administered intratumorally during each treatment. The therapy was repeated by using the same scheme if tumor recurrence was possible or if more than one lesion was present.

The patients were examined by means of PET the 1st day of percutaneous ethanol injection therapy. All patients were informed about the procedure, and written informed consent was obtained. The study was approved by our institutional review board. The PET study was performed after intratumoral administration of 37 MBq of 11C ethanol mixed with the dose of the unlabeled ethanol used for therapy. The dose of the unlabeled ethanol was determined by the oncologist on the basis of the tumor volume assessed at US. Dynamic data acquisition was used immediately following the administration of the tracer until up to 45 minutes after injection. Five 1-minute images followed by five 2-minute images and six 5-minute images were acquired for a total acquisition time of 45 minutes.

A scanner (PC 2048-7WB; Scanditronix, Uppsala, Sweden) with two ring detectors was used for the PET examinations. The system provides for the simultaneous acquisition of two primary sections and one secondary section. Each of the two rings has a 107-cm diameter, contains 512 bismuth germanate–gadolinium orthosilicate detectors (crystal size, 6 x 20 x 30 mm), and provides a field of view of 52 mm. The mean sensitivity for the two primary sections is 12,500 cps/µCi/mL and 17,500 cps/µCi/mL for the secondary section. The dead time loss is 10% at 30,000 cps per section. The evaluation of spatial linearity showed that the maximum displacement from the ideal source position was less than 0.4 mm in the whole field of view. Transmission scans with more than 10 million counts per section were obtained with a rotating germanium 68 pin source prior to the radionuclide administration to obtain cross sections for the attenuation correction of the acquired emission tomographic images.

The distribution and kinetics of the ethanol were investigated with 11C ethanol. The radiopharmaceutical is identical to unlabeled ethanol and may not be further metabolized after the intratumoral administration. The tracer was prepared without an added carrier by using a method described by Oberdorfer and Prenant (9). Quality control included high-pressure liquid chromatography. The 11C ethanol typically was obtained with a purity greater than 98% and the highest obtainable specific activity.

PET cross sections were reconstructed by using an iterative reconstruction algorithm with an image matrix of 256 x 256 because of the superior image quality (10). A 2-mm pixel size was chosen, and a resolution of 5.1 mm was obtained in the cross sections of the patients. All images were corrected for scatter and attenuation (11,12). Regions of interest were placed (A.D.S., L.G.S.) over the tumors and the normal liver parenchyma. All evaluated lesions were visible in at least two consecutive PET sections to minimize partial volume effects. The section showing the largest tumor diameter was used for the placement of the region of interest. The recovery coefficient for the system is 88% for lesions with a 1.5-cm diameter and the reconstruction program used in this study. Small lesions (less than 1.5 cm) were excluded from the evaluation.

The quantitative evaluation was based on the calculation of the standardized uptake values (13): standardized uptake value = tissue concentration (in megabecquerels per gram of tissue)/[injected dose (in megabecquerels)/body weight (in grams)]. The ratio of the 45-minute postinjection standardized uptake value to the 5-minute postinjection standardized uptake value was used to evaluate possible dilution of the ethanol in the target area.

Parametric imaging based on the Fourier transformation was applied to the dynamic data to evaluate the local distribution pattern of the ethanol. Phase and amplitude images of the first harmonic were calculated for each patient by using the dynamic data. The Fourier analysis was focused on the spatial change of the 11C activity in the tumor area and provided a more detailed visualization of the redistribution in the target area, thus avoiding the short-term artifacts that may be present on conventional images obtained immediately after the tracer injection. The amplitude images reflect the local maximum of the time-activity data for each pixel, while the phase images represent the interval when the local maximum was achieved.

For the graphic analysis of the data, we used the Statistica software package (StatSoft, Hamburg, Germany) on a personal computer (Pentium, 166 MHz, 64 MB RAM) running Windows NT 4.0 (Microsoft, Redmond, Wash). The software for the generation of Fourier images was developed by our group (L.G.S.) by using Visual C++ (Microsoft).


   RESULTS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
The visual evaluation of the 11C ethanol scans demonstrated a very high local accumulation of the tracer in the tumor and a very low tracer accumulation in the normal liver parenchyma during the examination. The distribution pattern of the 11C ethanol within the tumors was nearly homogeneous on the iteratively reconstructed PET scans (Fig 1). The normal liver parenchyma showed a substantial 11C uptake during the early phase in only one case. This was related to a slow outflow of ethanol via the puncture canal clearly visible on the PET images (Fig 2). Due to the outflow of the drug, the ethanol dose administered was suboptimal for therapy. This was recognized only with PET at the first therapeutic treatment.



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  		Figure 1. Patient 4. PET cross-sectional image obtained 10 minutes after the intratumoral administration of 11C ethanol. Focal accumulation of ethanol in the tumor with a homogeneous distribution is shown.

 


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  		Figure 2. Patient 3. PET cross-sectional image obtained 3 minutes after the intratumoral injection of 11C ethanol. Increased tracer accumulation in the tumor and a clearly visible outflow, which led to a suboptimal therapeutic dose, are shown. Because of monitoring by means of PET, a short-term correction of the dose administered was possible.

 
Time-activity curves of the tumor helped further evaluation of the ethanol kinetics (Fig 3). Five of eight tumors showed almost constant uptake values up to 45 minutes after injection after an initial distribution phase following intratumoral tracer injection (Fig 3). Three of eight tumors demonstrated a high 11C uptake immediately after the end of the ethanol injection followed by a rapid decrease in the 11C uptake during the 45-minute acquisition time (patients 1, 2, and 8) (Fig 3). The uptake values 5 minutes after injection exceeded those measured 45 minutes after injection and resulted in ratios of 0.18–0.67 (median value, 0.56) for the uptake at 45 minutes versus the uptake at 5 minutes (Fig 4a).



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  		Figure 3. Three-dimensional diagram of the time-activity data of 11C ethanol in all patients. The x axis represents the acquisition time in minutes, the y axis represents the patient number, and the z axis represents the 11C ethanol standardized uptake value (SUV). Note the rapid decrease in the tracer in patients 1, 2, and 8, which reflects a dilution of ethanol.

 


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  		Figure 4a. (a) Graph shows a comparison of the 5-minute and the 45-minute standardized uptake values (SUV) for 11C ethanol in all tumors. The tracer concentrations for the tumors are generally lower 45 minutes after injection compared with the 5-minute uptake values. (b) Graph shows a comparison of the 5-minute and the 45-minute standardized uptake values for 11C ethanol in the normal liver parenchyma. No major redistribution was observed in the liver.

 


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  		Figure 4b. (a) Graph shows a comparison of the 5-minute and the 45-minute standardized uptake values (SUV) for 11C ethanol in all tumors. The tracer concentrations for the tumors are generally lower 45 minutes after injection compared with the 5-minute uptake values. (b) Graph shows a comparison of the 5-minute and the 45-minute standardized uptake values for 11C ethanol in the normal liver parenchyma. No major redistribution was observed in the liver.

 
The 11C activity in the normal liver parenchyma was low in five of eight patients. The ratio of tumor activity to liver activity was 103:1–104:1. The time-activity curves of the normal liver parenchyma up to 45 minutes after injection gave evidence of a very slow increase in the tracer uptake with time, in some patients probably because of low ethanol elimination from the tumor cells. However, a large variation existed in the pattern of the time-activity curves. Even a substantial early uptake in the liver parenchyma was noted in one patient owing to suboptimal positioning of the puncture needle. In contrast to the tumor data (Fig 4a), the 5-minute uptake values did not necessarily exceed the 45-minute uptake values in normal liver parenchyma (Fig 4b). The ratio was 0.19–4.48 (median value, 0.57) for the uptake at 45 minutes versus the uptake at 5 minutes in the normal liver parenchyma. Three patients demonstrated ratios greater than 1.0.

Parametric imaging based on the Fourier transformation and the use of amplitude and phase images of the first harmonic demonstrated the distribution pattern of 11C ethanol in each tumor. Parametric images revealed a local accumulation of the tracer confined to the target area without a major washout to the liver parenchyma in all patients. In seven of eight tumors, inhomogeneous distribution patterns of the 11C ethanol were noted in the amplitude images (Fig 5). In six of eight tumors, phase images showed a redistribution of the tracer mainly to the peripheral parts of the tumors within the acquisition time (Fig 5). Slight redistribution was observed in two of eight tumors in the phase images (Fig 6).



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  		Figure 5. Patient 4. Magnification image of the tumor area. Amplitude image (left) and phase image (right) demonstrate a substantial redistribution of the 11C ethanol. The amplitude image shows an inhomogeneous distribution with several local maxima in the tumor periphery and defects in the central parts. The phase image clearly demonstrates a redistribution of the tracer toward the lateral parts of the tumor within the acquisition time. R = right.

 


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  		Figure 6. Patient 1. Magnification image of the tumor area. Amplitude image (left) and phase image (right) of the tumor region with a nearly homogeneous 11C ethanol distribution. This tumor does not show major minima of the tracer on the amplitude image. The ethanol distribution remains almost constant within the acquisition time. The phase image demonstrates a slight redistribution of the tracer to the lateral parts of the tumor periphery within the study time. R = right.

 

   DISCUSSION
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
Intratumoral percutaneous ethanol injection is a treatment recommended either as an effective therapy for small hepatocellular tumors or as a palliative treatment for unresectable liver tumors (1). Ethanol exerts its toxicity through cellular dehydration followed by coagulative thrombosis and through vascular thrombosis followed by occlusion. Livraghi et al (14) reported on complete necrosis in lesions smaller than 3.2 cm by using percutaneous ethanol injection. A problem in the therapy management of patients receiving percutaneous ethanol injection therapy is the lack of sensitive parameters for the early, noninvasive evaluation of the ethanol distribution, which is important for the assessment of response to therapy. It is known that measurements of several laboratory parameters, primarily tumor markers like {alpha}-fetoprotein, are not reliable for the evaluation of treatment efficacy, because only a minority of patients with small hepatocellular carcinomas exhibit an elevation of {alpha}-fetoprotein prior to the onset of treatment (1,15,16).

Several authors examined the value of morphologic imaging modalities, like US, CT, and MR imaging, for treatment monitoring. The authors tried to identify specific distribution patterns that are predictive for therapy response. Sironi et al (17) examined the role of US in patients with hepatocellular carcinomas and reported that hypoechoic lesions became hyperechoic and that hyperechoic tumors became homogeneous after treatment. However, other studies (18,19) showed that changes in US patterns do not reliably indicate tumor regression or progression.

Joseph et al (2) examined the contribution of CT in nine patients with biopsy-proved hepatocellular carcinomas and reported that four of five patients with CT evidence of necrosis had negative findings at biopsy and were free of known disease; however, none of the three patients with peripheral nodularity were disease free. These authors supposed that CT evidence of necrosis and lack of nodularity immediately after percutaneous ethanol injection are suggestive of absence of disease.

Most of the studies performed with morphologic imaging modalities focus on longer time intervals after treatment. Sironi et al (17) reported that a 6-month contrast-enhanced CT examination after treatment reliably indicated tumor recurrence. Similar results are reported for MR studies. Residual tumor tissue has a high signal intensity on T2-weighted MR images and corresponds to the contrast-enhanced areas on CT images (18). These results were not confirmed by other investigators. Nagel and Bernardino (3) examined 11 patients with hepatocellular carcinomas and concluded that the MR appearance of hepatic lesions treated by means of percutaneous ethanol injection is not a reliable indicator of residual tumor tissue. However, loss of enhancement may be indicative of tumor necrosis. The main problem with using CT or MR imaging for therapy management is the delayed detection of tumor viability and the lack of specific contrast enhancement.

PET with metabolically active substances like FDG has been found useful in a limited number of patients to evaluate their response to therapy. Highly differentiated primary hepatocellular carcinomas do not show any substantial enhancement of the FDG uptake prior to therapy (20). Therefore, it is difficult to delineate highly differentiated tumors accurately against the normal liver parenchyma. Another problem of FDG PET studies is the lack of specificity. An increase in FDG uptake can be related to viable tumor tissue, repair mechanisms, and areas of inflammation.

11C ethanol, which is identical to the unlabeled ethanol, is a suitable tracer for examining the distribution of the therapeutic substance in the target area during percutaneous ethanol injection therapy. It is assumed that a low elimination from the tumor tissue and a homogeneous tumor tissue distribution is a prerequisite for effective therapy. The labeled ethanol was mixed with the therapeutic dose of the nonlabeled drug for the accurate evaluation of the therapeutic situation. The time-activity curves of the tumor regions reflect the elimination of the ethanol. The visual evaluation was helpful in only one case in which a substantial 11C ethanol outflow was observed (Fig 2).

The 45 minute–to–5 minute ratio was used for the evaluation of ethanol dilution. The evaluation of all tumors revealed a ratio of less than 1.0, which suggests that dilution of ethanol is the standard observation after intratumoral administration. To our knowledge, no data are available in the literature about the absolute ethanol concentration in tumors. The median value for the 45 minute–to–5 minute ratio of 0.56 reflects an average dilution of approximately 50% of the initial concentration. Furthermore, the 45-minute values were less than one-third of the initial concentration values in three patients. The drug dilution must be taken into consideration when calculating the therapeutic dose. Further studies are required to assess the relation between ethanol concentration and tumor growth.

The use of parametric imaging was helpful for further image analysis. We chose the Fourier transformation to analyze the distribution pattern within the tumor area. Spectral analysis clearly showed an inhomogeneous distribution of the drug within the tumor region. To our knowledge, there are no comparable published studies focusing on the distribution of 11C ethanol in the target area. Some authors (1) used color Doppler US for real-time monitoring and to visualize the drug distribution.

However, Bartolozzi and Lencioni (1) emphasized in a recent review article that the use of color Doppler US as a final diagnostic test for therapy outcome is not appropriate but may be used to monitor the course of percutaneous ethanol injection treatment. Recognizable color Doppler signals within the lesion may be an indirect sign of residual tumor tissue. These authors recommend further evaluation with CT or MR imaging if the Doppler study results after percutaneous ethanol injection are negative. We emphasize that color Doppler US primarily permits measurement of the blood flow, which is not necessarily related to the ethanol distribution. In contrast, the use of PET with 11C ethanol allows a direct measurement of the drug kinetics in the target area.

Several factors that may limit the therapeutic effect of percutaneous ethanol injection, like tumor consistency, degree of vascularization, internal septa, presence of a tumor capsule, or the large amount of alcohol required for a sufficient inhibition of the tumor growth, are reported in the literature (1). Some authors report high vascularity of hepatocellular carcinoma (1,14), which may cause a rapid washout of the ethanol from the tumor cells and reduce the toxic effect of the ethanol.

The results of our study of PET with 11C ethanol do not support the hypothesis of a rapid washout for several reasons. First, the standardized uptake values of the tumor areas decreased very slowly with time but were still high even 45 minutes after tracer injection. Second, a redistribution to the normal liver parenchyma would be visible in the parametric phase images, which was not the case. Furthermore, phase images would appear relatively homogeneous if there was a rapid washout of the ethanol without any local redistribution pattern within the tumor.

Fourier analysis results support the hypothesis of tumor inhomogeneity for hepatocellular carcinomas, which is well known from histologic studies (1,15). The tumor texture seems to be different from that of normal liver parenchyma, partially solid and partially necrotic, and portions of the tumor parenchyma may be isolated by septa. This is supported by the parametric images that show an inhomogeneous distribution of the drug in the tumor and defects. Some investigators (1) tried to overcome the inhomogeneity by inserting two or three needles into each tumor lesion and performing multiple ethanol injections at several sites in one session. However, the effect of this procedure has to be evaluated in further studies.

In conclusion, two-thirds of the primary hepatocellular carcinomas included in this study demonstrated tracer distributions confined to the tumor, which is suggestive of a hard capsule. Drug dilution is an important factor that can be measured by means of PET and should be taken into consideration for the calculation of the therapeutic dose. The data give evidence of a substantial dilution (45 minute–to–5 minute ratio < 0.3) in a minority of patients (three of eight), who may be selected during the first treatment. According to these data, tumor texture and drug dilution are the most important factors in inhomogeneous drug distribution, which may not sufficiently inhibit tumor growth. While the data are helpful for optimizing therapy in individual patients, further studies are required to evaluate the routine use of 11C ethanol studies for treatment planning.


   Acknowledgments
 
We thank Dagmar Liebermann, MD, for fruitful discussion and Doris Chmielewski, technologist, of the Department of Oncological Diagnostics and Therapy, German Cancer Research Center, for her assistance in the patient studies.


   Footnotes
 
Abbreviation: FDG = 2-[fluorine 18]fluoro-2-deoxy-D-glucose

Author contributions: Guarantors of integrity of entire study, A.D.S., L.G.S., F.G.; study concepts, A.D.S., L.G.S., F.G., F.O.; study design, A.D.S., L.G.S.; definition of intellectual content, A.D.S., L.G.S.; literature research, A.D.S.; clinical studies, A.D.S., G.I., F.G.; data acquisition, A.D.S., G.K., F.O.; data analysis, A.D.S., L.G.S.; manuscript preparation and editing, A.D.S.; manuscript review, A.D.S., L.G.S., D.K.K., F.G., G.v.K.


   References
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Bartolozzi C, Lencioni R. Ethanol injection for the treatment of hepatic tumours. Eur Radiol 1996; 6:682-696.[Medline]
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  8. Dimitrakopoulou-Strauss A, Strauss LG, Schlag P, et al. Prediction of therapy response using PET and F-18-fluorouracil in patients with liver metastases from colorectal carcinoma. J Nucl Med 1998; 39:1197-1202.[Abstract/Free Full Text]
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