Brain Tumors

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This review addresses the specific contributions of nuclear medicine techniques, and especially positron emission tomography (PET), for diagnosis and management of brain tumors. 18F-Fluorodeoxyglucose PET has particular strengths in predicting prognosis and differentiating cerebral lymphoma from nonmalignant lesions. Amino acid tracers including 11C-methionine, 18F-fluoroethyltyrosine, and 18F-l-3,4-dihydroxyphenylalanine provide high sensitivity, which is most useful for detecting recurrent or residual gliomas, including most low-grade gliomas. They also play an increasing role for planning and monitoring of therapy. 18F-fluorothymidine can only be used in tumors with absent or broken blood–brain barrier and has potential for tumor grading and monitoring of therapy. Ligands for somatostatin receptors are of particular interest in pituitary adenomas and meningiomas. Tracers to image neovascularization, hypoxia, and phospholipid synthesis are under investigation for potential clinical use. All methods provide the maximum of information when used with image registration and fusion display with contrast-enhanced magnetic resonance imaging scans. Integration of PET and magnetic resonance imaging with stereotactic neuronavigation systems allows the targeting of stereotactic biopsies to obtain a more accurate histologic diagnosis and better planning of conformal and stereotactic radiotherapy.

Section snippets

18F-Fluorodeoxyglucose

The principle of the method by which PET using 18F-FDG permits the determination of regional cerebral metabolism was originally established by Sokoloff and colleagues as an autoradiographic technique and subsequently modified for PET.2 There is a high uptake of FDG in normal gray matter, mostly reflecting the metabolic demands of neuronal activity. Therefore, standard FDG-PET studies of the brain are being conducted under resting conditions. Quantitation of FDG uptake in brain and tumors can be

Amino Acids (PET and Single-Photon Emission Computed Tomography)

Besides FDG, radiolabeled amino acids are the most commonly used PET tracers for brain tumors. An advantage of using radiolabeled amino acids over FDG is the relatively low uptake of amino acids by normal brain tissue. Therefore, cerebral gliomas can be distinguished from the surrounding normal tissue with higher contrast compared with FDG. Many natural amino acids and their synthetic analogs have been labeled and explored as tumor imaging agents.39 Most PET studies of cerebral gliomas have

3′-Deoxy-3′-[18F]-Fluoro-(L)-Thymidine (FLT)

The thymidine nucleoside analog, 3′-deoxy-3′-[18F]-FLT, was developed as a molecular imaging probe to assess cellular proliferation in vivo with PET.95, 96 After FLT is transported into the cell, it is phosphorylated by thymidine kinase (TK-1) and trapped inside the cell.97 TK-1 is a cytosolic enzyme that is expressed during the DNA synthesis stage of the cell cycle. The rate-limiting step in FLT accumulation is phosphorylation by TK-1, causing FLT to accumulate in proportion to TK-1 activity.98

Other Radiopharmaceuticals

Several other single- and coincidence-photon–emitting radiopharmaceuticals have been used for diagnosing, grading, and monitoring brain tumors.

Summary and Perspectives

A broad range of tracers has been evaluated for clinical use in the diagnosis of brain tumors with PET or SPECT. The most widely available tracer, FDG, is a predictor of prognosis and is particularly useful for distinction of brain lymphoma from nonmalignant lesions. Image fusion with structural images (usually contrast-enhanced MRI) is increasingly becoming a standard technique. It is of particular value when reading FDG scans, which otherwise often provide little contrast between tumor and

References (142)

  • D. Salber et al.

    Differential uptake of [18F]FET and [3H]l-methionine in focal cortical ischemia

    Nucl Med Biol

    (2006)
  • M.D. Piroth et al.

    Prognostic value of early [18F]fluoroethyltyrosine positron emission tomography after radiochemotherapy in glioblastoma multiforme

    Int J Radiat Oncol Biol Phys

    (2011)
  • A. Salskov et al.

    FLT: Measuring tumor cell proliferation in vivo with positron emission tomography and 3′-deoxy-3′-[18F]fluorothymidine

    Semin Nucl Med

    (2007)
  • J. Toyohara et al.

    Basis of FLT as a cell proliferation marker: Comparative uptake studies with [3H]thymidine and [3H]arabinothymidine, and cell-analysis in 22 asynchronously growing tumor cell lines

    Nucl Med Biol

    (2002)
  • P. Kleihues et al.

    The WHO classification of tumors of the nervous system

    J Neuropathol Exp Neurol

    (2002)
  • M. Reivich et al.

    The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man

    Circ Res

    (1979)
  • R. Hustinx et al.

    Can the standardized uptake value characterize primary brain tumors on FDG-PET?

    Eur J Nucl Med

    (1999)
  • A.M. Spence et al.

    18F-FDG PET of gliomas at delayed intervals: Improved distinction between tumor and normal gray matter

    J Nucl Med

    (2004)
  • E. Prieto et al.

    Voxel-based analysis of dual-time-point 18F-FDG PET images for brain tumor identification and delineation

    J Nucl Med

    (2011)
  • L.L. Horky et al.

    Dual phase FDG-PET imaging of brain metastases provides superior assessment of recurrence versus post-treatment necrosis

    J Neurooncol

    (2011)
  • N.J. Patronas et al.

    Work in progress: [18F] fluorodeoxyglucose and positron emission tomography in the evaluation of radiation necrosis of the brain

    Radiology

    (1982)
  • G. Di Chiro et al.

    Cerebral necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors: PET and neuropathologic studies

    Am J Roentgenol

    (1988)
  • S.T. Chao et al.

    The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery

    Int J Cancer

    (2001)
  • T.P. Thompson et al.

    Distinguishing recurrent tumor and radiation necrosis with positron emission tomography versus stereotactic biopsy

    Stereotact Funct Neurosurg

    (1999)
  • P.E. Ricci et al.

    Differentiating recurrent tumor from radiation necrosis: Time for re-evaluation of positron emission tomography?

    Am J Neuroradiol

    (1998)
  • P.E. Valk et al.

    PET of malignant cerebral tumors after interstitial brachytherapyDemonstration of metabolic activity and correlation with clinical outcome

    J Neurosurg

    (1988)
  • D. Kahn et al.

    Diagnosis of recurrent brain tumor: Value of 201Tl SPECT vs 18F-fluorodeoxyglucose PET

    Am J Roentgenol

    (1994)
  • T. Ogawa et al.

    Clinical value of PET with 18F-fluorodeoxyglucose and l-methyl-11C-methionine for diagnosis of recurrent brain tumor and radiation injury

    Acta Radiol

    (1991)
  • K. Ericson et al.

    Positron emission tomography using 18F-fluorodeoxyglucose in patients with stereotactically irradiated brain metastases

    Stereotact Funct Neurosurg

    (1996)
  • O. Belohlávek et al.

    Brain metastases after stereotactic radiosurgery using the Leksell gamma knife: Can FDG PET help to differentiate radionecrosis from tumour progression?

    Eur J Nucl Med Mol Imaging

    (2003)
  • K. Van Laere et al.

    Direct comparison of 18F-FDG and 11C-methionine PET in suspected recurrence of glioma: Sensitivity, inter-observer variability and prognostic value

    Eur J Nucl Med Mol Imaging

    (2005)
  • Y. Sonoda et al.

    Clinical usefulness of 11C-MET PET and 201T1 SPECT for differentiation of recurrent glioma from radiation necrosis

    Neurol Med Chir (Tokyo)

    (1998)
  • Y. Terakawa et al.

    Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy

    J Nucl Med

    (2008)
  • N. Tsuyuguchi et al.

    Methionine positron emission tomography for differentiation of recurrent brain tumor and radiation necrosis after stereotactic radiosurgery—In malignant glioma

    Ann Nucl Med

    (2004)
  • G. Pöpperl et al.

    Value of O-(2-[18F]fluoroethyl)- l-tyrosine PET for the diagnosis of recurrent glioma

    Eur J Nucl Med Mol Imaging

    (2004)
  • T. Kuwert et al.

    Diagnosis of recurrent glioma with SPECT and iodine-123-alpha-methyl tyrosine

    J Nucl Med

    (1998)
  • H.G. Liu et al.

    F-18 FDG brain positron emission tomography and Tl-201 early and delayed SPECT in distinguishing atypical cerebral tumor from cerebral infarction

    Clin Nucl Med

    (2003)
  • F. Imani et al.

    Comparison of proton magnetic resonance spectroscopy with fluorine-18 2-fluoro-deoxyglucose positron emission tomography for assessment of brain tumor progression

    J Neuroimaging

    (2012)
  • G. Di Chiro et al.

    Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography

    Neurology

    (1982)
  • N.J. Patronas et al.

    Prediction of survival in glioma patients by means of positron emission tomography

    J Neurosurg

    (1985)
  • J.B. Alavi et al.

    Positron emission tomography in patients with gliomaA predictor of prognosis

    Cancer

    (1988)
  • T. Hölzer et al.

    FDG-PET as a prognostic indicator in radiochemotherapy of glioblastoma

    J Comput Assist Tomogr

    (1993)
  • H. Palmedo et al.

    FDG-PET in immunocompetent patients with primary central nervous system lymphoma: Correlation with MRI and clinical follow-up

    Eur J Nucl Med Mol Imaging

    (2006)
  • K. Makino et al.

    Does adding FDG-PET to MRI improve the differentiation between primary cerebral lymphoma and glioblastoma?Observer performance study

    Ann Nucl Med

    (2011)
  • N. Kosaka et al.

    18F-FDG PET of common enhancing malignant brain tumors

    Am J Roentgenol

    (2008)
  • J.M. Hoffman et al.

    FDG-PET in differentiating lymphoma from nonmalignant central nervous system lesions in patients with AIDS

    J Nucl Med

    (1993)
  • K. Villringer et al.

    Differential diagnosis of CNS lesions in AIDS patients by FDG-PET

    J Comput Assist Tomogr

    (1995)
  • J.A. Menendez et al.

    Use of fluorodeoxyglucose-positron emission tomography for the differentiation of cerebral lesions in patients with acquired immune deficiency syndrome

    Neurosurg Focus

    (2000)
  • M. Sathekge et al.

    Positron emission tomography in patients suffering from HIV-1 infection

    Eur J Nucl Med Mol Imaging

    (2009)
  • P.L. Jager et al.

    Radiolabeled amino acids: Basic aspects and clinical applications in oncology

    J Nucl Med

    (2001)

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