Choline Tracers for Imaging of Cancer

描述(由申请人提供)： 代谢成像技术，如正电子发射断层扫描(PET)，在肿瘤的诊断成像方面有着特别的前景。该项目的中心假设是，F-18标记的胆碱类似物可用作癌症PET成像的有用探针，因为它们是癌细胞中胆碱运输和磷酸化上调的良好示踪剂。我们还认为它们对甜菜碱衍生物的氧化代谢非常低，导致它们在体内的动力学简化。与C-11和F-18标记的胆碱类似物的初步工作显示，在前列腺癌和乳腺癌、脑肿瘤和肺结节患者中具有良好的实用价值。这项拟议的工作旨在阐明决定F-18胆碱放射性示踪剂在正常组织和恶性肿瘤组织中的分布的机制，并比较三种主要的F-18标记胆碱示踪剂的生化性质：氟甲基胆碱(FCH)、氟乙基胆碱(FECH)和氟甲基烯丙基胆碱(FMAC)。这项工作将为用放射性标记胆碱类似物解释肿瘤的PET成像研究提供更有力的基础，并为进一步开发临床显像剂选择最佳放射性示踪剂提供有用的数据。这项拟议的研究有三个具体目标：1)表征F-18标记的胆碱类似物与C-14胆碱在9L胶质瘤荷瘤大鼠肿瘤和几个正常组织中的转运和代谢，以及通过重组人CK酶的体外研究；2)阐明肿瘤对胆碱类似物的摄取与9L胶质瘤大鼠肿瘤灌注和胆碱转运的关系；以及3)比较放射性标记的2-氟-2-脱氧葡萄糖(FDG)和胸苷，评估F-18标记胆碱类似物在2种炎症动物模型中的摄取。

DESCRIPTION (provided by applicant): Metabolic imaging techniques, such as positron emission tomography (PET), hold particular promise for diagnostic imaging of neoplasms. The central hypothesis of this project is that F-18 labeled choline analogs may serve as useful probes for PET imaging of cancer because they are good tracers of choline transport and phosphorylation are upregulated in cancer cells. We also believe their oxidative metabolism to betaine derivatives is very low, resulting in a simplification of their in-vivo kinetics. Preliminary work with C-11 and F-18 labeled choline analogs have shown promising utility in patients with prostate and breast cancer, brain tumors, and pulmonary nodules. The proposed work seeks to clarify the mechanisms that determine the disposition of the F-18 choline radiotracers in normal and malignant tissues, and compare the biochemical properties of three leading F-18 labeled choline tracer candidates: fluoromethylcholine (FCH), fluoroethylcholine (FECH), and fluoromethylallylcholine (FMAC). The work should provide a stronger basis for interpreting PET imaging studies of cancer with radiolabeled choline analogs and provide useful data for the selection of an optimal radiotracer for further development as a clinical imaging agent. The proposed research has the three specific aims: 1) to characterize the transport and metabolism of F-18 labeled choline analogs in relationship to C-14 choline in tumor and several normal tissues in 9L glioma-bearing rats, and also by in-vitro studies with recombinant human CK enzyme; 2) to clarify the relationship of tumor uptake of choline analog to tumor perfusion, and choline transport in 9L glioma-bearing rats; and 3) to evaluate the uptake of F-18 choline analogs in 2 animal models of inflammation in comparison with radiolabeled 2-fluoro-2-deoxy-glucose (FDG) and thymidine.