DeGrado T R, Coleman R E, Wang S, Baldwin S W, Orr M D, Robertson C N, Polascik T J, Price D T
Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cancer Res. 2001 Jan 1;61(1):110-7.
The up-regulation of rates of choline uptake and phosphorylation in certain malignancies has motivated the development of positron-labeled choline analogues for noninvasive detection of cancer using positron emission tomography (PET). The choline analogue, no-carrier-added [18F]fluoromethyl-dimethyl-2-hydroxyethyl-ammonium (FCH), was synthesized through the intermediate [18F]fluorobromomethane. FCH was evaluated in relationship to 2-[18F]fluoro-2-deoxyglucose (FDG) as an oncological probe in cultured PC-3 human prostate cancer cells, a murine PC-3 human prostate cancer xenograft model, and in PET imaging studies of patients with prostate cancer. FCH was synthesized in 20-40% radiochemical yield and >98% radiochemical purity. Accumulation of FCH and FDG were comparable in cultured prostate cancer cells, whereas only FCH was inhibited (90%) by hemicholinium-3, a specific inhibitor of choline transport and phosphorylation. FCH showed similar biodistribution to [14C]choline in the tumor-bearing mouse, with prominent renal and hepatic uptake. Tumor uptake of FCH was similar to choline and FDG in the mouse model, although tumor:blood ratios were moderately higher for FCH. Initial PET imaging studies in prostate cancer patients showed high uptake of FCH in advanced prostate 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 uptake by normal tissues and prostate cancer neoplasms. FCH is potentially useful as a PET tracer for detection and localization of prostate cancer and monitoring effects of therapy.
某些恶性肿瘤中胆碱摄取和磷酸化速率的上调推动了正电子标记胆碱类似物的开发，用于使用正电子发射断层扫描（PET）对癌症进行无创检测。胆碱类似物，无载体添加的[18F]氟甲基 - 二甲基 - 2 - 羟乙基 - 铵（FCH），通过中间体[18F]氟溴甲烷合成。在培养的PC - 3人前列腺癌细胞、小鼠PC - 3人前列腺癌异种移植模型以及前列腺癌患者的PET成像研究中，对FCH作为肿瘤探针与2 - [18F]氟 - 2 - 脱氧葡萄糖（FDG）进行了评估。FCH的合成放射化学产率为20 - 40%，放射化学纯度>98%。在培养的前列腺癌细胞中，FCH和FDG的积累相当，而只有FCH被半胱氨酸 - 3（一种胆碱转运和磷酸化的特异性抑制剂）抑制（90%）。在荷瘤小鼠中，FCH的生物分布与[14C]胆碱相似，肾脏和肝脏摄取显著。在小鼠模型中，FCH的肿瘤摄取与胆碱和FDG相似，尽管FCH的肿瘤：血液比值略高。对前列腺癌患者的初步PET成像研究显示，晚期前列腺癌中FCH摄取高，并且检测到骨和软组织转移。在雄激素剥夺治疗期间重新扫描的患者中，肿瘤对FCH的摄取明显降低。结论是，FCH紧密模拟正常组织和前列腺癌肿瘤对胆碱的摄取。FCH作为PET示踪剂在前列腺癌的检测、定位和治疗效果监测方面具有潜在用途。
