Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Q J NUCL MED MOL IMAGING 2004;48:76-81 FULL CREDIT TO ALL MATERIAL TAKEN FROM THIS WEBSITE SHOULD BE GIVEN Position of nuclear medicine techniques in the diagnostic work-up of brain tumors A. DEL SOLE 1, R. MONCAYO 2, G. TAFUNI 3, G. LUCIGNANI 1, 4 Although any patient with a suspected brain tumor, either primary or metastatic, should be studied with anatomic imaging modalities such as angiography, computerized tomagraphy (CT) or magnetic resonance imaging (MRI), nuclear medicine techniques are available to further characterize some biological features of brain lesions and help in diagnosis and therapy planning. Bloob-brain-barrier disruption can be easily assessed with single-photon emission tomography (SPET), whereas focal metabolic changes can be better demonstrated by positron emission tomography (PET) as specific radiopharmaceuticals are available to detect changes in glucose utilization and aminoacid uptake with this technique. Expression of specific tumoral antigens is the basis of imaging with radioimmunoscintigraphy, a promising technique that can be applied to brain tumor therapy. The major clinical applications of nuclear medicine in the study of brain tumors — evaluation of the extension of a tumoral mass, differential diagnosis and evaluation of therapy and prognosis — are discussed. KEY WORDS: Brain neoplasms - Nuclear medicine Tomography, emission computed - Tomography, emission computed, single photon. I ntracranial brain neoplasms can be classified into primary brain tumors and metastatic tumors. Metastatic brain tumors are more common than primary brain tumors and are associated with lung neoplasms as well as breast, gastrointestinal, genitourinary tumors and melanomas. The basic classification of primary brain tumors by the World Health Organization (WHO) relies on their Address reprint requests to: Prof. G. Lucignani, Unit of Molecular Imaging, Department of Radiation Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milano. E-mail: giovanni.luciniani @unimi.it. 76 1 Institute of Radiological Sciences, University of Milan, Italy 2 University of Innsbruck, Innsbruck, Austria 3 IRCCS Ospetabe Maggiore Hospital, Polyclinic of Milan, Italy 4 Unit of Molecular Imaging, Department of Radiation Oncology European Institute of Oncology, Milan, Italy cellular origin, the clinical course and histological appearance of the neoplasms, immunophenotypic features and molecular/cytogenetic profile (Table I).1 Primary brain neoplasms which derive from neuroectoderm (primitive neuroectodermal tumor, PNET) are the most common, followed by tumors of meningeal, hematopoietic and nerve sheath origin. In adults the most frequent PNETs derive from glial cells (astrocyte, oligodendrocyte, ependymocytes and subependymocytes). In the Western world, the incidence of primary brain tumors depends on age and ranges between 1-10 cases/100 000 persons per year (age standardised). The distribution of tumor types for children and adults differs. In adults it is more frequent to find pituitary tumors, meningiomas, and glioblastomas. In children primitive neuroectodermal tumors, astrocytomas and pilocytic astrocytomas can be found. Non-nuclear medicine diagnostic procedures Most clinical manifestations of brain tumors are due to the “mass effect” of the growing tumor and can be detected when the tumor reaches the size of about 40 g. They consist of herniation syndromes, progressive THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING June 2004 DEL SOLE POSITION OF NUCLEAR MEDICINE TECHNIQUES IN THE DIAGNOSTIC WORK-UP OF BRAIN TUMORS TABLE I.—Revised classification of primary intracranial tumors according to WHO. Tumors of neuroepithelial tissue Astrocytic tumors, oligodendroglial tumors, mixed gliomas, ependymal tumors, choroid plexus tumors, glial tumors of uncertain origin, neuronal and mixed neuronal-glial tumors, neuroblastic tumors, pineal parenchyma, embryonal tumors Tumors of peripheral nerves Schwannoma, neurofibroma, perineuroma, malignant peripheral nerve sheath tumors Tumors of the meninges Tumors of meningothelial cells, mesenchymal non-meningothelial tumors, primary melanocytic lesions, tumors of uncertain histogenesis Lymphomas and hematopoietic neoplasms Malignant lymphoma, plasmacytoma, granulocytic sarcoma Germ cell tumors Germinoma, embryonal carcinoma, Yolk sac tumors, chorioncarcinoma, teratoma, mixed germ cell tumors Tumors of the sellar region Craniopharyngioma (adamantinomatous, papillary), granular cell tumor alterations of mentation and personality, headache and seizures. Other focal symptoms depend on the tumor location and include focal seizures, mental changes, visual disturbances, speech abnormalities, motor weakness, sensory disturbances, cranial nerve signs and gait abnormalities. Computerized tomography (CT) has been the first imaging modality that could directly visualize the presence of a brain tumor and is still widely used. Other radiological techniques have been applied to ascertain the presence of brain lesions more recently. Computerized tomography For many years, CT has been considered the gold standard in the diagnosis of brain tumors because it is able to demonstrate the presence of a brain lesion and define its dimensions and morphology and its relation with surrounding brain structure. It is also able to identify perilesional edema and define the number of brain lesions. This imaging technique is widely available and is useful when magnetic resonance imaging (MRI) cannot be used; CT is less degraded by artefacts due to motion of the patient for the short time of duration of the exam, but is less sensitive than MRI in brain regions that are near some bony areas of irregular shape, such as the posterior fossa and the floor of the middle fossa, due to the presence of beam-hardening artefacts and can miss non-enhancing tumors such as lowgrade gliomas. Contrast enhanced computerized tomography The administration of a contrast agent increases X-rays attenuation due to the high electron density of Vol. 48 - No. 2 the iodinated compounds. Contrast enhanced CT can detect blood-brain-barrier (BBB) disruption that occurs in many neurological disorders that include acute stroke, inflammatory and infectious cerebral diseases and multiple sclerosis. Moreover most brain tumors directly disrupt the blood-brain-barrier. Themselves, while in angiogenesis the BBB is absent. The region of contrast enhancement corresponds well with the main tumor mass. However, malignant tumor cells are commonly found beyond the enhanced portion of the tumor, particularly in gliomas. The type of enhancement can help in differentiating among lesions: contrast enhanced CT is still routinely used for the screening and follow-up of neoplasms. Cerebral multiple metastases, meningeal carcinomatosis, typical meningiomas or epidermoids can be diagnosed without further examinations. CT ability to represent bone structures makes this technique relevant in defining bone destruction or sclerosis associated with metastatic tumors, pituitary adenomas, meningiomas, adjacent carcinomas from the sinuses or pharynx, and in studying lesions with calcific components or localized close to bone structures. Magnetic resonance imaging MRI has several advantages as compared to CT. The technique has a higher contrast resolution and a lower occurrence of artefacts than CT, associated with the possibility of 3D-acquisition and reconstruction and a high spatial definition. These qualities permit an excellent resolution of brain regions that are poorly assessed by CT, such as infratentorial, sellar, temporal and meningeal regions. MRI studies are characterised by high sensitivity for structural alterations THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 77 POSITION OF NUCLEAR MEDICINE TECHNIQUES IN THE DIAGNOSTIC WORK-UP OF BRAIN TUMORS DEL SOLE caused by tumoral growth, that can further be TABLE II.—Radioisope uptake and histological grade of gliomas. enhanced by the use of paramagnetic contrast agents. Grade IV gliomas Grade III gliomas Low-grade tumors For these reasons, MRI is the procedure of choice for 1.4±1.5 1.04±2 imaging all types of brain tumors. MRI is particularly Thallium index 1.98±3.2 7.6±3.4 0.61±0.83 accurate in establishing the intra- or extra-axial origin BUdR of tumors; with a better definition it is possible to detect indirect signs (cortex dislocation, compression of sulci and cisterns, presence of cleavage plane for Nuclear medicine diagnostic procedures extrinsic lesions) and evaluate direct signs of neoNuclear medicine techniques were once used to plasia. A normal contrast-enhanced MRI scan essenconfirm the presence of a brain mass that was sustially rules out the possibility of a brain tumor. pected on a clinical basis. Nowadays, morphological imaging techniques, namely CT and MRI, are usually Angiography able to adequately demonstrate the presence of a The assessment of vascular structure as depicted brain lesion, to define its size and its relation with by angiography has largely lost its diagnostic role in surrounding brain structures and to identify direct or the work-up of brain tumors; a relevant exception is indirect signs that can assist in the diagnosis of brain represented by those lesions that are characterized tumor with a high degree of confidence. Nuclear medby an abnormal angiogenesis, such as hemangioblas- icine methods can assess and quantify biochemical tomas and meningiomas. At the moment angiogra- parameters in vivo, that are useful to further characphy has a complementary role in the pre-surgical terise brain neoplasms. assessment of neoplasms, providing information on the relationships between tumor and vessels. Studies of the blood-brain-barrier and Na/K pump Angiography is still relevant in the therapeutic phase Scintigraphic studies aimed at the detection of a of embolization of meningiomas or base of the skull leaky blood-brain-barrier can be useful in a variety of tumors or intra-arterial chemotherapy for gliomas. clinical situations including fever, toxins, and tumors. The routine use of angio-MR offers the possibility Without the disruption of the BBB tracer uptake will to complete a standard brain MR study adding infornot occur. Due to tumor growth, the BBB will be dismation on the relationships existing between tumor turbed allowing tracer uptake. Under these condiand vessels (encasement, venous compressions, etc.). tions some tracers, like 99mTc-DTPA and 301Tl-chloride The demonstration of small diameter vessels is still will show a significant. But the disruption of BBB is poor, with a consequent poor definition of tumoral not the only explanation of Thallium uptake, as it angiogenesis, but incoming technical amelioration accumulates in neoplastic tissues depending upon will soon widen angio-MR capabilities. blood-flow, cellular metabolism and efficiency of sodium-potassium ATPase. Magnetic resonance spectroscopy Initial studies on comparative tracer uptake in brain The separation of nuclear resonance frequencies tumors were carried out by Kaplan et al. 2 including of hydrogen, termed chemical shift, can define a spec- 29 patients with gliomas grade III and IV, of which 7 trum of signals that are a representation of the sever- could be studied post mortem. They found that 201Tl al chemical forms of hydrogen that are present in the gave the most accurate localization, 67Ga was good if volume studied. It is a non-invasive approach for the steroids were not being used, while 99mTc-GH could determination of some cerebral metabolites with clin- not differentiate fibrosis, non-fibrosis, necrosis and ical relevance, such as membrane phospholipids neoplasma. Similar data were presented by Mountz et (choline containing compounds) and respective degra- al. 3 An improvement in the technique was the use dation products, creatine and phosphocreatine (ele- of SPET. In a methodological paper Kim et al. 4 ments of cellular energetic metabolism), N-acetyl described semi-quantitative analysis of the results. aspartate and N-acetylate groups (marker of neuronal The best analysis method was mean counts in attenpopulation) and lactic acid (marker of hypoxic con- uation-corrected slices. They were able to show that dition). The technique is relatively insensitive because low-grade tumors had a lower uptake index as comit can only detect compounds that are present in con- pared to high-grade tumors: 1.20±0.40 vs. 2.40±0.61, centrations of about 1 mM. respectively. 78 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING June 2004 DEL SOLE POSITION OF NUCLEAR MEDICINE TECHNIQUES IN THE DIAGNOSTIC WORK-UP OF BRAIN TUMOURS A close relationship between Thallium uptake and proliferative activity was shown by Oriuchi et al. 5 They could demonstrate a positive correlation between bromodeoxyuridine (BUdR) and the 201Tl uptake index. Besides the tumor related index values, patients who died after surgery presented much higher values than survivors (Table II). Metabolic studies Metabolic studies aim at the detection of either tumor metabolism or of cell proliferation. For tumor metabolism both glucose utilisation (18F-FDG) and amino acids uptake (123I-IMT, 124I-IMT and other thyrosine derivatives, or 11C-methionine) can be used. Tracers for cell proliferation include 124I-deoxy uridine and 11C-2-thymidine. In a similar fashion as shown for 201Tl and BUdR, 123I-IMT uptake in gliomas appears to correlate with cellular density (light microscopy) and proliferative activtiy (Ki-67 nuclear antigen). Uptake indices for 123I-IMT are higher in cases of tumor recurrence as compared to patients without recurrence. Also 99mTc-SestaMIBI and 99mTcTetrofosmin concentrate in hypermetabolic processes such as tumors. STUDIES OF GLUCOSE METABOLISM Glucose utilization in tumors can be assessed using 2-[18F]Fluoro-2-deoxy-D-glucose (18F-FDG), which differs from glucose only for the replacement of an hydroxyl group with radioactive fluorine. Both 18F-FDG and glucose share the same carriers between the blood-brain-barrier. The accumulation of 18F-FDG, as detected by PET, is in proportion to glucose metabolic rate of the studied organ. It is well established that brain neoplasms present an increased glucose utilization respect to normal tissue, due to a high rate of glucose degradation into lactic acid even in presence of oxygen. Moreover, an over-expression of GLUT1 and GLUT3, members of the hexose transporter family, has been observed in several brain tumor types. 18F-FDG is able to identify the elevated glucose consumption in brain tumors, and it is now accepted that the uptake of the tracer correlates with the grade of malignancy of astrocytic tumors and also in oligodendrogliomas and gangliogliomas.6-8 On the other hand, low-grade gliomas are not easily identified or may appear as cold spots surrounded by normal high uptaking cerebral cortex, hampering a clear definition of tumor extension. Vol. 48 - No. 2 STUDIES OF AMINO ACIDS UPTAKE Imaging with radiolabeled amino acids visualizes protein synthesis and amino acid transport, which are accelerated in tumors. Methionine and other large neutral amino acids, are normally supplied to the brain from protein breakdown and diet through a transport system in the BBB; because the amino acids uptake in macrophages and other inflammatory cells is low, these tracers might be more tumor specific than 18F-FDG and difficult differential diagnoses with other cerebral pathologies, i.e., infections, radiation necrosis, edema, that may cause abnormal 18F-FDG uptake, can be avoided by using 11C-methionine (MET). 11C-methionine allows a earlier and more accurate delineation of the extension of the tumor boundaries than contrast-enhanced CT or MRI and is superior than 18F-FDG in delineating low-grade gliomas.9, 10 The use of 11C-methionine is justified by its relatively simple synthesis, rapid uptake in tumors and clearance from blood and other tissues. Other amino acids used for brain tumor imaging are tyrosine, thymidine, glutamate, phenylalanine and their labeled derivatives. Tyrosine uptake in brain tumors can be assessed with its labeled derivatives: O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET), L-[3-18F]-a-methyltyrosine (18F-FMT), [123I]iodo-α-methyltyrosine (123I-IMT). Also the uptake of tyrosine labeled derivatives is higher in brain tumors than in normal brain tissue. Other labeled amino acids for the evaluation of brain tumors include [18F]-fluorophenylalanine that has a marked uptake in oligodendrogliomas. Radioimmunoscintigraphy Some researchers have tested the feasibility of using monoclonal antibodies directed against neuroblastoma antigens, epidermal growth factor receptor, placental alcaline phosphatase, di-sialoganglioside GD2 and tenascin. A more elaborated construction has been reported using 99mTc-PnAO-Biotin together with an anti-tenascin antibody. More complex techniques have been proposed to enhance the signal-to-noise ratio, to overcome the limitations deriving from low tumor/non-tumor ratio and high dosimetry from the use of MoAbs directly labeled with Iodine-131. This technique has a good accuracy for the in vivo immunodetection of gliomas.11 THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 79 POSITION OF NUCLEAR MEDICINE TECHNIQUES IN THE DIAGNOSTIC WORK-UP OF BRAIN TUMOURS DEL SOLE TABLE III.—Role of various imaging modalities in different clinical settings in the work-up of primary brain tumors. Clinical question Imaging modality of choice CT and MRI Nuclear medicine Diagnosis of primary tumor Differential diagnosis Biological characterisation Pathology Treatment CT and MRI with contrast agent CT and MRI with contrast agent CT and MRI with contrast agent Refer to table in the text Neurosurgery radiation chemotherpy In AIDS patients: FDG-PET or 201Tl-SPET FDG-PET or MET-PET; if not available, 99mTcSestaMIBI or 201Tl-SPET Clinical indications Table III summarizes the role of various neuroimaging modalities in different clinical settings in patients with brain neoplasms. Identification of a brain tumor A direct sign of the presence of a brain tumor is the detection of an area with a density CT or MRI signal different from that of normal cerebral tissue, including changes secondary to contrast media infusion. Such changes are secondary to the structural features of neoplasms. Three main variables differentiate tumors from normal tissue: water content (due to the increased cellularity and interstitial fluids, that is, the cytotoxic intratumoral edema), regressive events (cysts, necrotic and hemorrhagic areas, calcifications, fat degenerative areas), vascular architecture (a feature of most tumors). Mass effect, edema and bone modifications are all indirect signs that can help in brain tumor detection. By combining direct and indirect signs, with intravenous contrast enhancement, brain tumor detection occurs with almost 100% accuracy with MRI. For these reasons, anatomical imaging procedures have become essential tools for brain tumor diagnosis. No patient presenting with symptoms suggesting the presence of a brain tumor can be assessed properly unless an X-ray CT and/or an MRI scan, with and without the administration of contrast agents and different acquisition sequences, in case of MRI, is performed. 80 Follow-up of the treated patients (clinically free from disease) In asymptomatic patients: CT and MRI with contrast agent every 3 months, alternating Restaging In symptomatic patients: CT or MRI with contrast agents and FDG-PET or MET-PET or (if PET not available) 99mTcSestaMIBI or 201Tl-SPET Monitoring of treatment response CT or MRI with contrast agent and FDG-PET or MET-PET or (if PET not available) 99mTcSestaMIBI or 201Tl-SPET Evaluation of the extension of the disease An accurate definition of the tumor boundaries is requested to plan an aggressive surgical treatment that should spare critical brain structures, such as the language areas. 11C-methionine is able to detect brain tumors boundaries, both in primary lesion and recurrence, with a high accuracy, regardless of their pathological grading.12 Also 201Tl and 123I-α-metyl-tyrosine can be used in this situation, but the limited spatial resolution of the SPET technique may restrict their value in the assessment of the extension of the disease. Differential diagnosis Differential diagnosis between brain tumors and benign lesions is usually based on clinical presentation, laboratory tests and different presentation in CT and MRI images. In AIDS patients, toxoplasmosis and primary intracerebral non-Hodgkin’s B cell lymphoma are both common and clinical presentation and laboratory tests are not useful to establish a correct diagnosis. In this setting, 201Tl can be helpful to demonstrate the presence of a malignant lesion as a focal accumulation of this tracer at the site of CT/MRI abnormality strongly suggests lymphoma, while the absence of uptake of 201Tl allows to exclude the diagnosis of lymphoma with a high degree of confidence.13 Guide for biopsy High grade brain tumors are characterised by the presence of an heterogeneous cellular composition for THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING June 2004 DEL SOLE POSITION OF NUCLEAR MEDICINE TECHNIQUES IN THE DIAGNOSTIC WORK-UP OF BRAIN TUMOURS the combination of active disease, non-specific inflammation, necrosis and edema. Both 18F-FDG and 11CMET can be used in the sterotactic environment to identify the areas of anaplasia or infiltration when a diagnostic biopsy is to be performed, in an effort to include the most malignant tissue in the pathologic specimen.14, 15 Follow-up EARLY ASSESSMENT OF THERAPY The assessment of presence of residual tumoral mass by means of CT or MRI is difficult in the early phase after surgical or radiant therapy, due to inflammatory reaction. 18F-FDG can differentiate residual tumor from the effect of therapy and a decline in 18FFDG uptake in a tumor weeks or months after therapy suggests a good response, indicating a reduced number of viable cells or reduced metabolism of damaged cells.16 LONG-TERM FOLLOW-UP Even several months after irradiation or chemotherapy for brain tumors, MRI and CT cannot easily distinguish tumor progression from radiation injury or necrosis. In high-grade tumors with elevated 18F-FDG uptake before treatment, focal uptake of 18F-FDG in areas of BBB breakdown detected by CT or MRI suggests the presence viable tumor cells, while absent FDG uptake suggests that necrosis is present.17 In low-grade gliomas, malignant transformation to high-grade tumors after treatment is not infrequent. The detection of areas of increased 18F-FDG uptake in histologically proven low-grade glioma predicts malignant transformation in such cases. PROGNOSIS In high-grade gliomas, the most powerful predictor of survival is pathological grading. In low-grade gliomas, the presence of areas of increased 18F-FDG uptake predicts, in most cases, a worse prognosis. Experience with other tracers is still limited, but a low uptake of 11C-methionine in the baseline study is associated with a longer survival. Vol. 48 - No. 2 References 1. Smirniotopoulos JG. The new WHO classification of brain tumors. Neuroimaging Clin N Am 1999;9:595-613. 2. Kaplan WD, Takvorian T, Morris JH, Rumbaugh CL, Connolly BT, Atkins HL. Thallium-201 brain tumor imaging: a comparative study with pathologic correlation. J Nucl Med 1987;28:47-52. 3. Mountz JM, Stafford SK, McKeever PE, Taren J, Beierwaltes WH. Thallium-201 tumor/cardiac ratio estimation of residual astrocytoma. J Neurosurg 1988;68:705-9. 4. Kim KT, Black KL, Marciano D, Mazziotta JC, Guze BH, Grafton S et al. Thallium-201 SPECT imaging of brain tumors: methods and results. J Nucl Med 1990;31:965-9. 5. Oriuchi N, Tamura M, Shibazaki T, Ohye C, Watanabe N, Tateno M et al. Clinical evaluation of thallium-201 SPECT in supratentorial gliomas: relationship to histologic grade, prognosis and proliferative activities [see comments]. J Nucl Med 1993;34:2085-9. 6. Kim CK, Alavi JB, Alavi A, Reivich M. New grading system of cerebral gliomas using positron emission tomography with F-18 fluorodeoxyglucose. J Neuro-Oncol 1991;10:85-91. 7. Mineura K, Shioya H, Kowada M, Ogawa T, Hatazawa J, Uemura K. Blood flow and metabolism of oligodendrogliomas: a positron emission tomography study with kinetic analysis of 18F-fluorodeoxyglucose. J Neuro-Oncol 1999;43:49-57. 8. Kincaid PK, El-Saden SM, Park SH, Goy BW. Cerebral gangliogliomas: preoperative grading using FDG-PET and 201Tl-SPECT. AJNR Am J Neuroradiol 1998;19:801-6. 9. Derlon JM, Petit-Taboue MC, Chapon F, Beaudouin V, Noel MH, Creveuil C et al. The in vivo metabolic pattern of low-grade brain gliomas: a positron emission tomographic study using 18F-fluorodeoxyglucose and 11C-L-methylmethionine. Neurosurgery 1997;40:276-87. 10. Kaschten B, Stevenaert A, Sadzot B, Deprez M, Degueldre C, Del Fiore G et al. Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med 1998;39:778-85. 11. Paganelli G, Magnani P, Zito F, Lucignani G, Sudati F, Truci G et al. Pre-targeted immunodetection in glioma patients: tumour localization and single-photon emission tomography imaging of [99mTc]PnAO-biotin. Eur J Nucl Med 1994;21:314-21. 12. Ogawa T, Inugami A, Hatazawa J, Kanno I, Murakami M, Yasui N et al. Clinical positron emission tomography for brain tumors: comparison of fluorodeoxyglucoseF18 and L-methyl-11C-methionine. AJNR Am J Neuroradiol 1996;17:345-53. 13. Lorbeboym M, Wallach F, Estok L, Mosesson RE, Sacher M, Kim CK et al. Thallium-201 retention in focal intracranial lesions for differential diagnosis of primary lymphoma and nonmalignant lesions in AIDS patients. J Nucl Med 1998;39:1366-9. 14. Hanson MW, Glantz MJ, Hoffman JM, Friedman AH, Burger PC, Schold SC et al. FDG-PET in the selection of brain lesions for biopsy. J Compux Assist Tomogr 1991;15:796-801. 15. Goldman S, Levivier M, Pirotte B, Brucher JM, Wikler D, Damhaut P et al. Regional methionine and glucose uptake in high-grade gliomas: a comparative study on PET-guided stereotactic biopsy. J Nucl Med 1997;38:1459-62. 16. Hanson MW, Hoffman JM, Glantz MJ. FDG-PET in the early postoperative evaluation of patients with brain tumor. J Nucl Med 1990;31:799. 17. Di Chiro G, Oldfield E, Wright DC, De Michele D, Katz DA, Patronas NJ et al. Cerebral necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors: PET and neuropathologic studies. AJR Am J Radiol 1988;150:189-97. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 81