Radiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online before print September 19, 2002, 10.1148/radiol.2252011431
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2252011431v1
225/2/567    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Riemann, B.
Right arrow Articles by Schober, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Riemann, B.
Right arrow Articles by Schober, O.
(Radiology 2002;225:567-574.)
© RSNA, 2002

Neuroradiology

Noninvasive Grading of Untreated Gliomas: A Comparative Study of MR Imaging and 3-(Iodine 123)-L-{alpha}-methyltyrosine SPECT1

Burkhard Riemann, MD, Karsten Papke, MD, Norbert Hoess, MD, Torsten Kuwert, MD, Matthias Weckesser, MD, Peter Matheja, MD, Hansdetlef Wassmann, MD, Walter Heindel, MD and Otmar Schober, MD, PhD

1 From the Departments of Nuclear Medicine (B.R., M.W., P.M., O.S.), Clinical Radiology (K.P., W.H.), and Neurosurgery (N.H., H.W.), University of Münster, Albert-Schweitzer-Strasse 33, 48129 Münster, Germany; and Department of Nuclear Medicine, University of Erlangen-Nürnberg, Germany (T.K.). Received August 27, 2001; revision requested October 17; final revision received April 8, 2002; accepted April 26. Address correspondence to B.R. (e-mail: riemanb@uni-muenster.de).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To compare the accuracy of magnetic resonance (MR) imaging scores with that of 3-(iodine 123)-L-{alpha}-methyltyrosine (123I-IMT) single photon emission computed tomography (SPECT) in the noninvasive grading of untreated gliomas.

MATERIALS AND METHODS: The study comprised 15 patients with low-grade gliomas (grades I-II, according to World Health Organization criteria) and 33 patients with high-grade gliomas (grades III-IV). The lesions were evaluated by using an MR imaging score based on nine criteria. The 123I-IMT uptake was quantified as the ratio between the amino acid uptake in the tumor and that in the contralateral hemisphere. To test for potentially significant differences in diagnostic performance between contrast material–enhanced MR imaging and 123I-IMT SPECT, binormal receiver operating characteristic curves were fitted to the data and compared by using the area test.

RESULTS: The accuracy of MR imaging in the noninvasive grading of untreated gliomas was higher than that of 123I-IMT SPECT (88% vs 79%). However, the difference in diagnostic performance was not significant on the basis of findings at receiver operating characteristic analysis (P > .2). Neither MR imaging nor 123I-IMT SPECT allowed differentiation between high-grade gliomas (grades III and IV).

CONCLUSION: Although 123I-IMT uptake is significantly higher in high-grade gliomas than in low-grade gliomas, the performance of 123I-IMT SPECT adds little to the accuracy of determining tumor grade when MR imaging is performed.

© RSNA, 2002

Index terms: Brain neoplasms, 10.363 • Brain neoplasms, MR, 10.12143, 10.12146 • Brain neoplasms, radionuclide studies, 10.12162 • Brain neoplasms, SPECT, 10.12162


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Gliomas are the most common primary tumors of the central nervous system and represent about one-third of all intracranial tumors in adults (1). The therapeutic management and prognosis in patients with gliomas depend on the reliable distinction between high- and low-grade gliomas (2). A variety of imaging modalities has been evaluated in the accurate identification of glioma grade and clinical characteristics (3). Since the descriptions published by Damadian and his colleagues, there have been many attempts to determine the malignancy of tumors by using magnetic resonance (MR) imaging scores (4,5). Asari et al (6) have successfully applied an MR imaging score to determine the histopathologic malignancy grade of astrocytomas. This score was based on the following nine criteria: heterogeneity, cyst formation or necrosis, hemorrhage, tumor crossing the midline, edema and/or mass effect, definition of border, flow void, degree of contrast material enhancement, and heterogeneity of contrast enhancement.

In addition, functional imaging procedures, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), have received considerable attention in this context. PET with fluorine 18 (18F) fluorodeoxyglucose (FDG) (7,8) or carbon 11 (11C) methionine (9–12) enhancement is thought to be useful for the evaluation of the degree of malignancy of cerebral gliomas, but contradictory results have been reported (13–15). In addition, PET is expensive and has only limited availability. Since 1989, SPECT with the radiolabeled amino acid 3-(iodine 123)-L-{alpha}-methyltyrosine (123I-IMT) has become a promising new tool for imaging amino acid transport rates in brain tumors. The 123I-IMT SPECT is valuable in the delineation of tumor extent (16–18) and the early detection of tumor recurrence (19). In addition, 123I-IMT SPECT has been applied successfully in the noninvasive grading of brain tumors (20–22).

To our knowledge, no clinical studies have been performed to date to compare MR imaging and 123I-IMT SPECT in the evaluation of the histologic grade of gliomas. It was the aim of our study to compare the accuracy of MR imaging scores with that of 123I-IMT SPECT in the noninvasive grading of untreated gliomas.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
From 1994 until 1999, 48 adults (20 women, 28 men; mean age ± SD, 54 years ± 15; age range, 19–86 years) with untreated gliomas underwent MR imaging and 123I-IMT SPECT at the University of Münster.

Diagnosis was verified by means of histopathologic examination in all patients. Open surgery (29 patients) and stereotactic biopsy (19 patients) were performed an average of 6.4 days after SPECT (range, 0–21 days) and 7.8 days after MR imaging (range, 0–35 days).

Histopathologic assessment according to the criteria of the revised World Health Organization, or WHO, classification (23) revealed one grade I pilocytic astrocytoma, 10 grade II astrocytomas, one grade II astro-oligodendroglioma, one grade II oligoastrocytoma, one grade II pleomorphic xanthoastrocytoma, one grade II subependymoma, nine grade II astrocytomas, 23 grade IV astrocytomas, and one grade IV medulloblastoma.

Informed consent was obtained from all patients. The study protocol was approved by the ethical committee of the Westfälische Wilhelms-Universität Münster.

MR Imaging Data Acquisition
MR images were obtained with a 1.5-T system prior to stereotactic biopsy or open surgery in all patients (6). A spin-echo pulse sequence was applied to obtain transverse T1-weighted 630/15 (repetition time msec/echo time msec) and T2-weighted 2,700/90 images. A 256 x 256 matrix was used with a 5-mm section thickness; field of view was 25 cm. Contrast material–enhanced T1-weighted images were obtained in all patients by using 0.1 mmol per kilogram of body weight of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany).

The nine MR imaging criteria of Asari et al (6), including heterogeneity, cyst formation or necrosis, hemorrhage, tumor crossing the midline, edema and/or mass effect, border definition, flow void, and the degree and heterogeneity of contrast enhancement, were scored (K.P.) without knowledge of the grade of the tumor (Table 1). The distinction between "mild or slight," "moderate," and "marked or severe" was made by means of visual assessment. The MR imaging scores were averaged for each patient and for each criterion to yield the mean MR imaging scores, which were then subjected to statistical analysis (see below).


View this table:
[in this window]
[in a new window]

  		TABLE 1. MR Imaging Criteria and Scores

 
SPECT Data Acquisition
Details of the performance of 123I-IMT SPECT in our laboratory have been described previously (20).

After patients fasted overnight, SPECT was performed by using a triple-headed camera (MULTISPECT 3; Siemens Gammasonics, Erlangen, Germany) equipped with medium-energy collimators. Thyroid uptake of possible free radioiodine was blocked with sodium perchlorate. Imaging was started 10 minutes after intravenous injection of 185 MBq of 123I-IMT, which was synthesized and purified as reported previously (24). Ninety-six images (three sets of 32 images; 3.75° per step), each registered over 60 seconds, were recorded into a 128 x 128 matrix format that corresponded to a pixel dimension of 3.56 x 3.56 mm on a 360° rotation. Transverse images were reconstructed without prefiltering by using filtered backprojection. Attenuation correction was first order, according to the method of Chang (25). In-plane resolution of the reconstructed images was 13 mm full width at half maximum, as measured with a Jaszczak phantom (26); section thickness was approximately 7 mm.

As described previously, uptake indices of the tumors were calculated by using a three-dimensional technique to display the images (MPI-Tool; Advanced Tomo Vision, Kerpen, Germany) (17,22). Briefly, the intensity of the background was characterized by the mean and SD of the 123I-IMT uptake in the hemisphere not affected by the tumor. In case of midline tumors, the background region was drawn over the anterior or posterior half of the brain. The isocontour around the tumor was defined automatically by using a threshold value two SDs above the mean background activity. The 123I-IMT uptake index of the tumor was then determined by calculating the ratio between the maximum tumor uptake and the mean background uptake.

In patients in whom tumors could not be differentiated from normal cerebral uptake, the uptake index was set to 1.00, as reported previously (22).

Data Analysis
All values are given as mean ± SD. Differences between groups were tested by means of one-way factorial analysis of variance before the unpaired Student t test was used for statistical analysis. Analyses of correlation between MR imaging and 123I-IMT SPECT were performed by using Pearson correlation coefficients and multiple regression analysis (SPSS Base software, version 10.0; SPSS, Chicago, Ill).

Thresholds of discrimination between high- and low-grade gliomas, yielding maximum diagnostic accuracy, were determined iteratively. Accuracy, sensitivity, and specificity values were then calculated by using standard formulas.

To test for potentially significant differences in diagnostic performance between contrast-enhanced MR imaging and 123I-IMT SPECT, binormal receiver operating characteristic curves were fitted to the data and compared by using the area test (ROCKIT 0.9 B software; C. Metz, Chicago, Ill) (27).

For statistical analysis, the only low-grade glioma (grade I, patient 1) was included in the low-grade glioma group I–II.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Representative images are shown in Figures 1 and 2. The mean MR imaging scores for all patients and the 123I-IMT uptake indices are given in Table 2.



View larger version (62K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Patient 3. Left: Transverse SPECT image shows 123I-IMT uptake in a left temporo-occipital astrocytoma (grade II). On the middle transverse T2-weighted 2,700/90 MR image, the same tumor (arrow) appears hypointense. On the right transverse gadolinium-enhanced T1-weighted 630/15 MR image, the tumor shows no contrast enhancement.

 


View larger version (28K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2. Patient 32. Left: Transverse SPECT image shows 123I-IMT uptake in a right frontal astrocytoma (grade IV, patient 32). On the middle transverse T2-weighted 2,700/90 MR image, the partly cystic and partly necrotic tumor (arrows) appears inhomogenous. On the right transverse T1-weighted gadolinium-enhanced 630/15 MR image, the tumor shows marked contrast enhancement.

 

View this table:
[in this window]
[in a new window]

  		TABLE 2. Patient Data

 
MR Imaging
The mean MR imaging scores for all patients were 0.80 ± 0.36 (range, 0.22–1.56) for grades I and II gliomas, 1.31 ± 0.29 (range, 0.89–1.78) for grade III gliomas, and 1.53 ± 0.40 (range, 0.67–2.11) for grade IV gliomas (Fig 3). Low-grade gliomas had a significantly lower value than that of high-grade gliomas (grade III, P < .01; grade IV, P < .001); however, there was no significant difference between high-grade gliomas (grades III and IV, P > .05).



View larger version (21K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3. Graph shows correlation between the mean MR imaging score of all patients and the histopathologic grade. Mean values ± SDs (vertical lines) were 0.80 ± 0.36 in grades I and II gliomas, 1.31 ± 0.29 in grade III gliomas, and 1.53 ± 0.40 in grade IV gliomas. Dots represent individual untreated gliomas.

 
The iteratively determined threshold of discrimination between low-grade (grades I–II) and high-grade (grades III–IV) gliomas, yielding the maximum accuracy, was 1.00 for the mean MR imaging score. By using this threshold, contrast-enhanced MR imaging enabled correct identification of tumor grade in 30 of 33 patients with high-grade gliomas (grades III–IV; sensitivity, 91%) and in 12 of 15 patients with low-grade gliomas (grades I–II; specificity, 80%) (Table 2). This corresponded to an accuracy value of 88% for contrast-enhanced MR imaging.

The mean MR imaging scores for only three of the nine criteria (cyst formation or necrosis and degree and heterogeneity of contrast enhancement) were significantly lower (P < .05) in grades I and II gliomas than in grade III gliomas. Accordingly, there were significant differences between these criteria (cyst formation or necrosis, P < .05; degree and heterogeneity of contrast enhancement, P < .01) in grades I and II gliomas and grade IV gliomas. However, there were no significant differences among the criteria in high-grade gliomas (grades III and IV; P > .05).

A multiple regression equation was formulated for identification of tumor grade (y), in which numeric values are multiplied by the respective MR imaging scores indicated for each of the nine criteria in parentheses: y = 1.784 + 0.199 (heterogeneity) + 0.124 (cyst formation or necrosis) + 0.121 (hemorrhage) - 0.139 (tumor crossing the midline) - 0.232 (edema and/or mass effect) + 0.312 (border definition) + 0.253 (flow void) + 0.469 (degree of contrast enhancement) - 0.032 (heterogeneity of contrast enhancement). The degree of contrast enhancement was a statistically significant indicator (P < .01) of the pathologic tumor grade (Table 3).


View this table:
[in this window]
[in a new window]

  		TABLE 3. Multiple Regression Analysis

 
123I-IMT SPECT
The relative 123I-IMT uptake indices were 1.91 ± 0.73 (range, 1.00–3.75) in grades I and II gliomas, 2.71 ± 1.01 (range, 1.85–4.99) in grade III gliomas, and 2.70 ± 0.72 (range, 1.87–4.38) in grade IV gliomas (Fig 4). Low-grade gliomas (grades I-II) had a significantly lower value than that of high-grade gliomas (grade III, P < .05; grade IV, P < .01); however, again there was no significant difference between high-grade gliomas (grades III and IV, P > .05).



View larger version (21K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4. Graph shows correlation between the 123I-IMT uptake index of all patients and the histopathologic grade. Mean values ± SDs (vertical lines) were 1.91 ± 0.73 in grades I and II gliomas, 2.71 ± 1.01 in grade III gliomas, and 2.70 ± 0.72 in grade IV gliomas. Dots represent individual untreated gliomas.

 
123I-IMT SPECT failed to depict four low-grade gliomas, since the tumor uptake was not elevated compared with that of background activity. In these cases, the uptake index was set to 1.00. Three of these tumors showed no focally increased 123I-IMT uptake (patients 5, 14, and 15). Patient 11 showed an increased 123I-IMT accumulation within a left temporal hemorrhage but normal 123I-IMT uptake in a right frontal grade II astrocytoma. This patient had sustained the intracranial hemorrhage during an accident 19 days before 123I-IMT SPECT was performed.

The threshold of discrimination between low- and high-grade gliomas, yielding the maximum accuracy, was 2.10 for the 123I-IMT uptake indices. By using this threshold, 123I-IMT SPECT allowed correct identification in 28 of 33 patients with high-grade gliomas (grades III-IV; sensitivity, 85%) and 10 of 15 patients with low-grade gliomas (grades I-II; specificity, 67%). This corresponded to an accuracy value of 79% for 123I-IMT SPECT.

Relationship between MR Imaging and 123I-IMT SPECT
The malignancy grade of gliomas was significantly related to the mean MR imaging scores (r = 0.64, P < .001) and the 123I-IMT uptake indices (r = 0.45, P < .01).

However, the mean MR imaging scores and the 123I-IMT uptake indices showed a poor but significant correlation (r = 0.31, P < .05; Fig 5). By using multiple regression analysis, the 123I-IMT uptake index correlated only weakly with the degree of contrast enhancement (r = 0.37, P < .01).



View larger version (23K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 5. Graph shows mean MR imaging score and amino acid uptake in untreated gliomas. Line A denotes the threshold of discrimination between high- and low-grade gliomas for the mean MR imaging score, and line B denotes the corresponding threshold for 123I-IMT SPECT. Dots indicate individual untreated gliomas. Diagonal line represents linear regression.

 
The accuracy of the mean MR imaging score (88%) was higher than that of the 123I-IMT uptake index (79%). However, the binormal receiver operating characteristic analysis of the data revealed no statistically significant difference between the diagnostic performance of contrast-enhanced MR imaging and 123I-IMT SPECT (P > .2) (Fig 6). Overall accuracy in the noninvasive grading of untreated gliomas was not enhanced if MR imaging and 123I-IMT SPECT data were combined (accuracy, 88%; sensitivity, 100%; specificity, 60%).



View larger version (29K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 6. Receiver operating characteristic curve for discrimination between patients with high- and low-grade gliomas by using the mean MR imaging score and the 123I-IMT uptake index. The areas under the curves are commonly used to evaluate the quality of a diagnostic test independent of an arbitrarily chosen threshold of discrimination. The areas under the curves were 0.90 for the mean MR imaging score and 0.81 for the 123I-IMT uptake index. There was no statistically significant difference between the receiver operating characteristic curves for both diagnostic procedures (area test value = 1.2551; P = .21).

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
The neurosurgical care and prognosis of patients with cerebral gliomas are dependent on the accurate definition of tumor grade (28,29).

MR Imaging
By using primarily morphologic imaging modalities, such as MR imaging, a close correlation has been found between intense gadopentetate dimeglumine enhancement of cerebral astrocytomas and histologic areas of malignant neovascularity and endothelial proliferation (30). Therefore, contrast enhancement is associated with a higher grade of malignancy (31,32). However, the importance of abnormalities in T1 and T2 relaxation times for distinguishing benign from malignant brain tumors remains controversial (33,34). To our knowledge, no commonly accepted MR imaging score has been defined to date with regard to the determination of the malignancy grade of gliomas.

In 1990, Dean et al (35) introduced an MR imaging score system based on seven criteria for the noninvasive grading of astrocytomas. This scoring system was modified by Asari and colleagues in 1994 (6). They found that the mean MR imaging scores in 41 patients with supratentorial astrocytomas were significantly different between low-grade (grade II) and high-grade (grade III) astrocytomas, as well as between high-grade astrocytomas (grades III and IV).

In the present study, this MR imaging score was applied to 48 patients with gliomas to identify the tumor grade with the use of MR imaging. The data revealed a significant difference between the mean MR imaging scores of low-grade (grades I–II) and high-grade (grades III–IV) gliomas.

In contrast to Asari et al (6), no further discrimination was possible between high-grade gliomas (grades III and IV). However, they did not calculate accuracy values for the discrimination between different histopathologic tumor grades. For this reason, it is difficult to compare the results from Asari et al (6) with the present data or with those of other studies.

In the present study, the mean MR imaging scores for all nine criteria were lower in low-grade gliomas (grades I–II) than in high-grade gliomas (grades III–IV). However, only three of the criteria (cyst formation or necrosis and degree and heterogeneity of contrast enhancement) reached statistical significance. Presumably, this is because the nine criteria differ in their potential to allow identification of tumor grade. Therefore, multiple regression analysis could be helpful to establish a rank order of potency of the nine criteria to further improve the differentiation between high- and low-grade malignancy.

123I-IMT SPECT
For 2 decades, functional imaging with PET and SPECT has been widely applied in the molecular imaging of brain tumors (18). PET with 18F FDG provides a useful assay for the noninvasive grading of gliomas (7,8). In this regard, PET with 11C methionine has yielded contradictory results (10,12,15,36). However, PET is expensive and has only limited availability. Therefore, research efforts have been concentrated on the development of radiopharmaceuticals suitable for imaging the metabolism of brain tumors with SPECT (14,37).

In 1989, the radiolabeled amino acid 123I-IMT was introduced as a SPECT radiopharmaceutical in neuro-oncology. 123I-IMT is metabolically stable and is not incorporated into proteins (38). Its transport into gliomas is mediated by the specific carrier system for large neutral amino acids (L system) and is not dependent on blood-brain barrier disruptions (39–41). 123I-IMT SPECT has been applied successfully in the delineation of tumor extent (16–18) and the early detection of tumor recurrence (19).

In addition, Matheja et al (22) have shown that the combination of thallium 201 SPECT and 123I-IMT SPECT can distinguish different histopathologic brain tumor entities, such as gliomas, lymphomas, and nonneoplastic lesions. A correlation between 123I-IMT uptake and the proliferative activity of gliomas has been demonstrated in vitro and in vivo (41,42). Results of initial clinical studies have suggested that 123I-IMT SPECT is a promising new tool for the determination of the histopathologic malignancy grade of gliomas: The accuracy of 123I-IMT SPECT in distinguishing low- and high-grade gliomas is in the range of 75% to 83% (20–22). These figures are in accordance with those of the present study, which yielded an accuracy of 79%. However, Bader et al (43) have found no significant correlation between 123I-IMT uptake and the histopathologic grade of recurrent gliomas. This may indicate that recurrent gliomas have an altered amino acid transport rate compared with that of untreated gliomas.

In the present patient population, 123I-IMT SPECT did not allow discrimination between high-grade gliomas (grades III and IV), which is in agreement with results of previous studies (20–22). This could be due in part to a disparity in the biopsy methods in the various tumor groups, since four of nine grade III astrocytomas but only six of 23 grade IV gliomas were diagnosed by means of needle biopsy. In addition, 123I-IMT SPECT failed to depict four low-grade gliomas (patients 5, 11, 14, and 15). Patient 11 showed increased 123I-IMT accumulation in a left temporal hemorrhage but normal 123I-IMT uptake in a right frontal grade II astrocytoma. This patient had experienced a cerebral contusion 19 days before 123I-IMT SPECT was performed. Therefore, the increased 123I-IMT accumulation in the intracranial hemorrhage may be attributed to nonspecific 123I-IMT uptake due to a disruption of the blood-brain barrier (36). For these reasons, 123I-IMT SPECT images should not be interpreted without knowledge of morphologic data in clinical settings.

Relationship between MR Imaging and 123I-IMT SPECT
To our knowledge, no clinical studies have been performed to date to compare the accuracy of 123I-IMT SPECT with that of primarily morphologic imaging procedures like computed tomography (CT) or MR imaging with regard to the noninvasive grading of gliomas.

In the present study, no statistically significant difference could be demonstrated between the abilities of contrast-enhanced MR imaging and 123I-IMT SPECT to allow differentiation between high- and low-grade malignancy in untreated gliomas. The accuracy of MR imaging (88%), however, was higher than that of 123I-IMT SPECT (79%). Concordantly, overall accuracy in the noninvasive grading of gliomas was not improved if MR imaging and 123I-IMT SPECT data were combined. Thus, in noninvasive grading, 123I-IMT SPECT seems to add little to the diagnostic accuracy of MR imaging.

Nevertheless, 123I-IMT SPECT should not be omitted from the initial workup of patients with brain tumors. Results of numerous clinical studies (15,18,44,45) have shown that the tumoral distribution of amino acids surpasses the extent of contrast enhancement in CT and MR imaging. Therefore, PET and SPECT with radiolabeled amino acids may be of considerable value for the exact delineation of tumor extent prior to interventional therapy, as well as for the direction of stereotactic biopsies performed on the most proliferatively active parts of the tumor (12,16,44,45). In addition, it has been shown that the 123I-IMT uptake index is of prognostic relevance for patients with brain tumors (46).

In the present study, there was only a weak correlation between the mean MR imaging score and the 123I-IMT uptake index. This may be due in part to the fact that two methodologically distinct imaging procedures (ie, primarily morphologic and functional techniques) were compared: In contrast to the nonspecific accumulation of gadopentetate dimeglumine, the transport of 123I-IMT into gliomas is mediated by specific carrier systems and is not dependent on disruptions of the blood-brain barrier (39–41). Furthermore, there was a great difference in the number of parameters investigated: MR images are interpreted on the basis of a variety of distinct parameters, whereas 123I-IMT SPECT interpretation depends merely on the uptake index. In addition, the striking difference in image resolution, which is 1.0 mm for MR imaging and 13.0 mm for 123I-IMT SPECT, emphasizes the inequality of these imaging procedures; in the present study, however, the mean size of the gliomas was 3.79 cm and thus relatively large as compared with image resolution.

Limitations
Certain subtypes of gliomas, such as gangliogliomas, oligodendrogliomas, and pilocytic astrocytomas, have been reported to show unusual MR imaging appearances and significantly increased amino acid uptake rates as compared with those of most gliomas of the astrocytoma series (12,47). Since only one pilocytic astrocytoma and two mixed oligoastrocytomas were present in our patient population, our results may not be transferred to these rare glioma subtypes. Further studies are required to focus on the noninvasive grading of these subtypes of gliomas.

A further drawback of the present study is the difference in the number of low- and high-grade gliomas. However, the patient population reflects the prevalence of low- and high-grade gliomas in adults (1). The fact that only one person was involved in the analysis of the MR imaging and 123I-IMT SPECT data is an additional study limitation.

In summary, our data indicate that the accuracy of MR imaging in the distinction of high- and low-grade malignancy in untreated gliomas is higher than that of 123I-IMT SPECT. In addition, overall accuracy in the noninvasive grading of gliomas is not improved if MR imaging and 123I-IMT SPECT data are combined. Therefore, the performance of 123I-IMT SPECT adds little to determining tumor grade when MR imaging is performed.

This does not imply that contrast-enhanced MR imaging and 123I-IMT SPECT are of equal value with regard to other indications—for example, the correct delineation of tumor extent and the early diagnosis of tumor recurrence after treatment. Further studies are needed to compare the utility and the therapeutic effect of primarily morphologic and functional imaging techniques to improve the diagnostic workup of patients with brain tumors. This is of particular importance because of the use of image fusion and newly developed hybrid scanners that combine SPECT or PET and CT or MR imaging, which may improve decision making.


   ACKNOWLEDGMENTS
 
The authors express their gratitude to S. Steinhoff from the Department of Nuclear Medicine, University of Münster, Germany, for her help with the SPECT camera and to G. Goder from the Institute of Medical Informatics and Biometrics, University of Münster, Germany, for support with the statistical analysis.


   FOOTNOTES
 
Abbreviation: IMT = 3-(iodine 123)-L-{alpha}-methyltyrosine

Author contributions: Guarantor of integrity of entire study, O.S.; study concepts, B.R., K.P., T.K.; study design, N.H., H.W., O.S.; literature research, B.R.; clinical studies, B.R., K.P., N.H.; data acquisition, B.R., K.P., N.H., M.W., P.M.; data analysis/interpretation, K.P., M.W., P.M., W.M.; statistical analysis, B.R.; manuscript preparation, B.R.; manuscript definition of intellectual content, N.H., P.M., H.W., W.H.; manuscript editing, B.R., K.P.; manuscript revision/review, K.P., T.K., M.W., O.S.; manuscript final version approval, all authors.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 

  1. Ben-Schlomo Y, Davey Smith G. Brain tumour trends. Lancet 1989; 2:1272-1273.[Medline]
  2. Schmidek HH. Surgical management of supratentorial gliomas. In: Schmidek HH, Sweet WH, eds. Operative neurosurgical techniques. 3rd ed. Philadelphia, Pa: Saunders, 1995; 517-534.
  3. Byrne TN. Imaging of gliomas. Semin Oncol 1994; 21:162-171.[Medline]
  4. Damadian R. Tumor detection by nuclear magnetic resonance. Science 1971; 171:1151-1153.[Abstract/Free Full Text]
  5. Goldsmith M, Koutcher J, Damadian R. Application of the NMR malignancy index to human gastro-intestinal tumors. Cancer 1978; 41:183-191.[CrossRef][Medline]
  6. Asari S, Makabe T, Katayama S, Itoh T, Tsuchida S, Ohmoto T. Assessment of the pathological grade of astrocytic gliomas using an MRI score. Neuroradiology 1994; 36:308-310.[CrossRef][Medline]
  7. Di Chiro G, DeLaPaz RL, Brooks RA, et al. Glucose utilization of cerebral gliomas measured by 18-F-fluorodeoxyglucose and positron emission tomography. Neurology 1982; 32:1323-1329.[Abstract/Free Full Text]
  8. Delbeke D, Meyerowitz C, Lapidus RL, et al. Optimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of low-grade from high-grade brain tumors with PET. Radiology 1995; 195:47-52.[Abstract/Free Full Text]
  9. Sasaki M, Kuwabara Y, Yoshida T, et al. A comparative study of thallium-201 SPET, carbon-11 methionine PET and fluorine-18 fluorodeoxyglucose PET for the differentiation of astrocytic tumours. Eur J Nucl Med 1998; 25:1261-1269.[CrossRef][Medline]
  10. Ogawa T, Shishido F, Kanno I, et al. Cerebral glioma: evaluation with methionine PET. Radiology 1993; 186:45-53.[Abstract/Free Full Text]
  11. Derlon JM, Chapon F, Noel MH, et al. Non-invasive grading of oligodendrogliomas: correlations between in vivo metabolic pattern and histopathology. Eur J Nucl Med 2000; 27:778-787.[CrossRef][Medline]
  12. Herholz K, Hölzer T, Bauer B, et al. 11C-methionine PET for differential diagnosis of low-grade gliomas. Neurology 1998; 50:1316-1322.[Abstract/Free Full Text]
  13. Tyler JL, Diksic M, Villemure JG, et al. Metabolic and hemodynamic evaluation of gliomas using positron emission tomography. J Nucl Med 1987; 28:1123-1133.[Abstract/Free Full Text]
  14. Oriuchi N, Tomiyoshi K, Inoue T, et al. Independent thallium-201 accumulation and fluorine-18-fluorodeoxyglucose metabolism in glioma. J Nucl Med 1996; 37:457-462.[Abstract/Free Full Text]
  15. Tovi M, Lilja A, Bergström M, Ericsson A, Bergström K, Hartman M. Delineation of gliomas with magnetic resonance imaging using Gd-DTPA in comparison with computed tomography and positron emission tomography. Acta Radiol 1990; 31:417-429.[Medline]
  16. Weckesser M, Griessmeier M, Schmidt D, et al. Iodine-123 {alpha}-methyl tyrosine single-photon emission tomography of cerebral gliomas: standardised evaluation of tumour uptake and extent. Eur J Nucl Med 1998; 25:150-156.[CrossRef][Medline]
  17. Weckesser M, Matheja P, Rickert C, et al. Evaluation of the extension of cerebral gliomas by scintigraphy. Strahlenther Onkol 2000; 176:180-185.[CrossRef][Medline]
  18. Langen KJ, Weckesser M. Recent advances of PET in the diagnosis of brain tumors. Front Radiat Ther Oncol 1999; 33:9-22.[Medline]
  19. Kuwert T, Woesler B, Morgenroth C, et al. Diagnosis of recurrent glioma with SPECT and iodine-123-{alpha}-methyl tyrosine. J Nucl Med 1998; 39:23-27.[Abstract/Free Full Text]
  20. Kuwert T, Morgenroth C, Woesler B, et al. Uptake of iodine-123-{alpha}-methyl tyrosine by primary brain tumors and non-neoplastic brain lesions. Eur J Nucl Med 1996; 23:1345-1353.[CrossRef][Medline]
  21. Woesler B, Kuwert T, Morgenroth C, et al. Non-invasive grading of primary brain tumours: results of a comparative study between SPET with 123I-{alpha}-methyl tyrosine and PET with 18F-deoxyglucose. Eur J Nucl Med 1997; 24:428-434.[Medline]
  22. Matheja P, Rickert C, Weckesser M, et al. Sequential scintigraphic strategy for the differentiation of brain tumours. Eur J Nucl Med 2000; 27:550-558.[CrossRef][Medline]
  23. Kleihues P, Burger PC, Scheithauer BW. Histological typing of tumours of the central nervous system WHO international classification of tumours. 2nd ed. Berlin, Germany: Springer, 1993.
  24. Machulla HJ, Skansdal A, Stöcklin G. 123(125)Xe-exposed KIO3, a reagent for iodination with high specific activity. Radioclin Acta 1977; 24:42-46.
  25. Chang LT. A method for attenuation correction in radionuclide computed tomography. IEEE Trans Nucl Sci 1978; NS-25:638-643.
  26. Jaszczak RJ, Greer KL, Floyd CE, Jr, Harris CC, Coleman RE. Improved SPECT quantification using compensation for scattered photons. J Nucl Med 1984; 25:893-900.[Abstract/Free Full Text]
  27. Metz CE. ROC methodology in radiologic imaging. Invest Radiol 1986; 21:720-733.[Medline]
  28. Schmidek HH. Surgical management of supratentorial gliomas. In: Schmidek HH, Sweet WH, eds. Operative neurosurgical techniques. 3rd ed. Philadelphia, Pa: Saunders, 1995; 517-534.
  29. Glantz MJ, Burger PC, Herndon JE, et al. Influence of the type of surgery on the histologic diagnosis in patients with anaplastic gliomas. Neurology 1991; 41:1741- 1744.[Abstract/Free Full Text]
  30. Earnest F, Kelly PJ, Scheithauer BW, et al. Cerebral astrocytomas: histopathologic correlation of MR and CT contrast enhancement with stereotactic biopsy. Radiology 1988; 166:823-827.[Abstract/Free Full Text]
  31. Tchang S, Scotti G, Terbrügge K, et al. Computerized tomography as a possible aid to histological grading of supratentorial gliomas. J Neurosurg 1977; 46:735-739.[Medline]
  32. Joyce P, Bentson J, Takahashi M, Winter J, Wilson G, Byrd S. The accuracy of predicting histologic grades of supratentorial astrocytomas on the basis of computerized tomography and cerebral angiography. Neuroradiology 1978; 16:346-348.[CrossRef][Medline]
  33. Mills C, Crooks L, Kaufman L, Brant-Zawadzki M. Cerebral abnormalities: use of calculated T1 and T2 magnetic resonance imaging for diagnosis. Radiology 1984; 150:87-94.[Abstract/Free Full Text]
  34. Just M, Thelen M. Tissue characterization with T1, T2 and proton density values: results in 160 patients with brain tumors. Radiology 1988; 169:779-785.[Abstract/Free Full Text]
  35. Dean BL, Drayer BP, Bird CR, et al. Gliomas: classification with MR imaging. Radiology 1990; 174:411-415.[Abstract/Free Full Text]
  36. Roelcke U, Radü E, Ametamey S, Pellikka R, Steinbrich W, Leenders KL. Association of 82rubidium and 11C-methionine uptake in brain tumors measured by positron emission tomography. J Neurooncol 1996; 27:163-171.[Medline]
  37. Black KL, Hawkins RA, Kim KT, Becker DP, Lerner C, Marciano D. Use of thallium-201 SPECT to quantitate malignancy grade of gliomas. J Neurosurg 1989; 71:342-346.[Medline]
  38. Langen KJ, Coenen HH, Roosen N, et al. SPECT studies of brain tumors with L-3-[123I]iodo-{alpha}-methyltyrosine: comparison with PET, 124IMT and first clinical results. J Nucl Med 1990; 31:281-286.[Abstract/Free Full Text]
  39. Langen KJ, Roosen N, Coenen HH, et al. Brain and brain tumor uptake of L-3-[123I]iodo-{alpha}-methyl tyrosine: competition with natural L-amino acids. J Nucl Med 1991; 32:1225-1229.[Abstract/Free Full Text]
  40. Riemann B, Kopka K, Stögbauer F, et al. Kinetic parameters of 3-[123I]iodo-L-{alpha}-methyl tyrosine ([123I]IMT) transport in human GOS3 glioma cells. Nucl Med Biol 2001; 28:293-297.[CrossRef][Medline]
  41. Langen KJ, Mühlensiepen H, Holschbach M, Hautzel H, Jansen P, Coenen HH. Transport mechanisms of 3-[123I]iodo-{alpha}-methyl-L-tyrosine in a human glioma cell line: comparison with [3H-methyl]-L-methionine. J Nucl Med 2000; 41:1250- 1255.[Abstract/Free Full Text]
  42. Kuwert T, Probst-Cousin S, Woesler B, et al. Iodine-123-alpha-methyl tyrosine in gliomas: correlation with cellular density and proliferative activity. J Nucl Med 1997; 38:1551-1555.[Abstract/Free Full Text]
  43. Bader JB, Samnick S, Moringlane JR, et al. Evaluation of L-3-[123I]iodo-{alpha}-methyltyrosine SPECT and [18F]fluorodeoxyglucose PET in the detection and grading of recurrences in patients pretreated for gliomas at follow-up: a comparative study with stereotactic biopsy. Eur J Nucl Med 1999; 26:144-151.[CrossRef][Medline]
  44. Bergström M, Collins VP, Ehrin E, et al. Discrepancies in brain tumor extent as shown by computed tomography and positron emission tomography using [68Ga]EDTA, [11C]glucose, and [11C]methionine. J Comput Assist Tomogr 1983; 7:1062-1066.[Medline]
  45. Mosskin M, Ericson K, Hindmarsh T, et al. Positron emission tomography compared with magnetic resonance imaging and computed tomography in supratentorial gliomas using multiple stereotactic biopsies as reference. Acta Radiol 1989; 30:225-232.[Medline]
  46. Weckesser M, Matheja P, Schwarzrock A, et al. Prognostic significance of amino acid transport imaging in patients with brain tumors. Neurosurgery 2002; 50:958-964.[CrossRef][Medline]
  47. Weckesser M, Matheja P, Rickert CH, et al. High uptake of L-3 [123I]iodo-{alpha}-methyl tyrosine in pilocytic astrocytomas. Eur J Nucl Med 2001; 28:273-281.[CrossRef][Medline]



This article has been cited by other articles:


Home page
 JNMHome page
C. Plathow and W. A. Weber
Tumor Cell Metabolism Imaging
J. Nucl. Med., June 1, 2008; 49(Suppl_2): 43S - 63S.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
G. T. Smith, F. Isidoro, J. A. Thie, K. F. Hubner, B. Riemann, K. Papke, N. Hoess, G. Goder, T. Kuwert, M. Weckesser, et al.
Optimal Diagnosis by Using Two-Marker Studies [letter] * Dr Riemann and colleagues respond:
Radiology, July 1, 2003; 228(1): 292 - 293.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2252011431v1
225/2/567    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Riemann, B.
Right arrow Articles by Schober, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Riemann, B.
Right arrow Articles by Schober, O.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
RADIOLOGY RADIOGRAPHICS RSNA JOURNALS ONLINE