Tr. Degrado et al., Synthesis and evaluation of F-18-labeled choline as an oncologic tracer for positron emission tomography: Initial findings in prostate cancer, CANCER RES, 61(1), 2001, pp. 110-117
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.