Diagnosis of primary brain tumors

M. Cimitan

Research output: Contribution to journalArticlepeer-review


MRI and CT are the dominant imaging modalities for delineating brain structures and MRI is widely considered as the gold standard to characterize tumors and distinguish benign from malignant lesions. Unfortunately, anatomical imaging techniques cannot provide information about tumor grade. This is an important piece of information, since brain tumors are frequently heterogeneous. Furthermore, tumors such as gliomas tend to have infiltrative borders which are not accurately defined by MRI or CT. Positron emission tomography (PET) is a neuroimaging technique that provides information concerning metabolic features of tumors. 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) is the most widely available PET tracer for tumor imaging. Malignant brain tumors, like many other soft tissue tumors, show increased glucose metabolism which is reflected on FDG PET imaging. In the evaluation of primary brain tumors, FDG PET is useful to obtain information about tumor grade and prognosis. Moreover, FDG PET is a very sensitive imaging modality for evaluating lymphoma in the central nervous system and evaluating HIV positive patients to differentiate patients with central nervous system (CNS) lymphoma from patients with CNS infection. However, the normal brain has high glucose metabolism and a very high background accumulation of FDG in FDG PET assessment. Furthermore, FDG PET occasionally fails to distinguish radiation necrosis from recurrent disease. Radiopharmaceuticals other than FDG were found to be potentially useful for PET imaging of brain tumor physiology. These include the radiotracers of amino acid metabolism, nucleotide metabolism, and membrane lipid synthesis. The IIC-methionine (MET) and radiolabeled tyrosine are the radiolabeled amino acids most commonly used in clinical PET. MET PET was proven to be more accurate for detection of tumor recurrences and differentiation of brain tumors from non neoplastic lesions than CT and MRI. Moreover, MET was found to be better than FDG in the delineation of tumor margins, in differentiating tumor recurrence from radiation injuries, and predicting the histological grade and prognosis of gliomas. However, the application of MET PET remains limited to a few PET centres as the short physical half-life of 11C (20 minutes) necessitates an on-site cyclotron. Recently, O-(-2-18F-fluoroethyl)-L-tyrosine (FET) was developed for PET imaging of tumor cells; this has the advantage of a longer physical half-life (110 minutes) than 11C. The uptake and image contrast of FET in brain tumors appear to be very similar to those of MET. FET PET was valuable to distinguish between post-therapeutic benign lesions and tumor recurrence after initial treatment of low- and high-grade gliomas. Particularly, FET uptake was higher in recurrent gliomas than in radiation injuries, whereas MRI showed a limited specificity in differentiating between post-therapeutic unspecific changes and neoplastic lesions. Differences in the dynamics of FET uptake between recurrent low- and high-grade gliomas allow discrimination between these two prognostically different groups. At the same time, 11C-radiolabeled thymidine has been developed as an in vivo radiotracer of DNA synthesis. In patients with brain tumors with less 11C-thymidine uptake than FDG uptake, tumor progression was slower than in patients with both high 11C-thymidine and FDG uptake. Subsequently, 18F-labeled thymidine (FIT) has been developed by virtue of its longer half-life (110 minutes) over the 11C-labeled analogues (20 minutes). In side-by-side studies of the same patient, the absolute uptake (SUVmax) of FLT was low but image con-trast was better compared to FDG PET. FLTSUVmax correlated much better with the Ki-67 index (P <0.0001) than FDG SUVmax (P <0.07). FLT PET visualized all high grade tumors (grade III or IV) but grade 11 tumors did not show significant FLT uptake. Furthermore, the sensitivity of FLT to detect gliomas of different grades was lower than that of MET (78.3% vs 91.3%) especially for low grade astrocytamas. High uptake of IIC-choline was reported in brain tumors. The synthesis of membrane phospholipids is increased in certain malignancies and this is reflected in choline metabolism. IIC-choline PET was able to differentiate between low grade and high grade gliomas but not differentiate low grade gliomas from non neoplastic lesions. Just like 11C-choline, 18F-fluorocholine (FCH) which has a longer physical half-life, readily accumulates in brain tumors and shows low background uptake in the normal brain. 18F-choline was found to be slightly superior to 11C-choline with regard to the tumor/normal brain ratio. Similar to FET. FCH is a promising tracer for separating radiation necrosis from tumor recurrence. Uptake of these two tracers in radiation injuries is generally lower than their uptake in tumors. FET accumulation in radiation lesions is most likely due to a disruption of the blood-brain barrier alone whereas FCH is additionally trapped by macrophages. Brain tumors, Glioma, PET imaging.

Original languageEnglish
Pages (from-to)55-66
Number of pages12
JournalRivista Medica
Issue number4
Publication statusPublished - Dec 2007

ASJC Scopus subject areas

  • Medicine(all)

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