Choline Tracers for Imaging of Cancer

用于癌症成像的胆碱示踪剂

• 批准号: 6916589
• 负责人: Timothy R. DeGrado
• 金额: $ 30.47万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6916589
• 关键词: bioimaging /biomedical imaging; biological transport; blood chemistry; carbon; choline; deoxyglucose; fluorine; high performance liquid chromatography; inflammation; kidney metabolism; laboratory rat; liver metabolism; neoplasm /cancer; neoplasm /cancer radiodiagnosis; neoplasm /cancer radionuclide diagnosis; pharmacokinetics; phosphorylation; positron emission tomography; radionuclides; radiotracer; technology /technique development; thin layer chromatography; thymidine; urinalysis

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.

描述（由申请人提供）： 代谢成像技术，例如正电子发射断层扫描 (PET)，对于肿瘤的诊断成像具有特殊的前景。该项目的中心假设是，F-18 标记的胆碱类似物可以作为癌症 PET 成像的有用探针，因为它们是胆碱转运的良好示踪剂，并且癌细胞中的磷酸化上调。我们还相信它们对甜菜碱衍生物的氧化代谢非常低，从而简化了它们的体内动力学。 C-11 和 F-18 标记的胆碱类似物的初步研究表明，它在前列腺癌、乳腺癌、脑肿瘤和肺结节患者中具有良好的应用前景。拟议的工作旨在阐明决定 F-18 胆碱放射性示踪剂在正常和恶性组织中的分布的机制，并比较三种主要 F-18 标记胆碱示踪剂候选物的生化特性：氟甲基胆碱 (FCH)、氟乙基胆碱 (FECH)和氟甲基烯丙基胆碱 (FMAC)。这项工作应该为解释放射性标记胆碱类似物的癌症 PET 成像研究提供更强有力的基础，并为选择最佳放射性示踪剂以进一步开发为临床成像剂提供有用的数据。拟议的研究具有三个具体目标：1) 表征 F-18 标记胆碱类似物与 9L 胶质瘤荷瘤大鼠肿瘤和几种正常组织中 C-14 胆碱的转运和代谢，并通过体外研究重组人 CK 酶的研究； 2) 阐明肿瘤摄取胆碱类似物与肿瘤灌注和9L胶质瘤荷瘤大鼠中胆碱转运的关系； 3) 与放射性标记的 2-氟-2-脱氧葡萄糖 (FDG) 和胸苷相比，评估 2 种炎症动物模型中 F-18 胆碱类似物的摄取情况。