Clinical impact of amino acid PET in gliomas.

Abstract

With an incidence of 20.5 per 100,000 people each year, tumors of the central nervous system are a heterogeneous group, with meningiomas (35.5%) and gliomas (30%) being the most common (1). Although 97% of meningiomas are benign, 54% of gliomas are highly malignant glioblastomas of World Health Organization (WHO) grade IV. Survival rates are 35.7% at 1 y and 4%–7% at 5 y for glioblastoma, 60%–80% at 1 y and 26%–46% at 5 y for astrocytomas and oligodendrogliomas of WHO grade III, and 94% at 1 y and 67% at 5 y for astrocytomas and oligodendrogliomas of WHO grade II (2). Additionally, the central nervous system may be invaded by metastases from other malignancies. Brain tumors create structural lesions whose diagnosis is primarily dependent on imaging with CT and MR. However, it is possible to improve clinical management by using PET to provide physiologic and biochemical information on tumor metabolism, proliferation rate, and invasiveness, as well as to determine the relationship of the tumor to important functional tissue and to monitor the effects of treatment (3). Imaging of brain tumors with 18 F-FDG was the first oncologic application of PET. As in other malignancies, glucose consumption is increased in brain tumors, especially in malignant gliomas, but differentiating tumors from normal tissue or nontumorous lesions is often difficult because of the high metabolism in normal cortex. 18 FFDG uptake in low-grade tumors is usually similar to that in normal white matter, and uptake in high-grade tumors can be less than or similar to that in normal gray matter. The sensitivity of detection of lesions is further decreased by the high variance of 18 F-FDG uptake and its heterogeneity within a single tumor. Labeled amino acids and their analogs are particularly attractive for imaging brain tumors because of the high uptake in tumor tissue and low uptake in normal brain. This increased amino acid uptake, especially in gliomas, is not a direct measure of protein synthesis or dependent on blood–brain barrier breakdown but rather is related to increased transport mediated by type L amino acid carriers: facilitated transport is upregulated because of the increased transporter expression in tumor vasculature (4). Additionally, the countertransport system A is overexpressed in neoplastic cells and seems to correlate positively with the rate of tumor cell growth (5). Therefore, elevated transport of amino acids not only is a result of increased protein synthesis but also reflects the increased demand by different types of metabolism in the tumor cell. The most frequently used radiolabeled amino acid is methyl- 11 CL-methionine (MET) (6,7). Especially in low-grade gliomas, amino acid uptake is related to prognosis a nd survival. With regard to tumor extentandinfiltrationintosurroundingtissue,assessmentofaminoacid uptake is superior to measurement of glucose consumption (8 )a nd