Synthesis and evaluation of F-18-labeled choline as an oncologic tracer for positron emission tomography: Initial findings in prostate cancer

The up-regulation of rates of choline uptake and phosphorylation in certain malignancies has motivated the development of positron-labeled choline ana logues for noninvasive detection of cancer using positron emission tomograp hy (PET). The choline analogue, no-carrier-added [F-18]fluoromethyl-dimethy l-2-hydroxyethyl (FCH), was synthesized through the intermediate [F-18]fluo robromomethane. FCH was evaluated in relationship to 2-[F-18]fluoro-2-deoxy glucose (FDG) as an oncological probe in cultured PC-3 human prostate cance r cells, a murine PC-3 human prostate cancer xenograft model, and in PET im aging studies of patients with prostate cancer. FCH was synthesized in 20-4 0% radiochemical yield and >98% radiochemical purity. Accumulation of FCH a nd FDG were comparable in cultured prostate cancer cells, whereas only FCH was inhibited (90%) by hemicholinium-3, a specific inhibitor of choline tra nsport and phosphorylation. FCH showed similar biodistribution to [C-14]cho line in the tumor-bearing mouse, with prominent renal and hepatic uptake. T umor uptake of FCH was similar to choline and FDG in the mouse model, altho ugh tumor:blood ratios were moderately higher for FCH. Initial PET imaging studies in prostate cancer patients showed high uptake of FCH in advanced p rostate carcinoma and detection of osseous and soft tissue metastases. FCH uptake by tumors was markedly reduced in patients rescanned during androgen deprivation therapy. It is concluded that FCH closely mimics choline uptak e by normal tissues and prostate cancer neoplasms. FCH is potentially usefu l as a PET tracer for detection and localization of prostate cancer and mon itoring effects of therapy.