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），持有肿瘤的诊断成像的特别承诺。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，并且磷酸化在癌细胞中上调。我们还认为它们氧化代谢为甜菜碱衍生物的能力非常低，导致其体内动力学简化。用C-11和F-18标记的胆碱类似物的初步工作已经显示出在患有前列腺癌和乳腺癌、脑肿瘤和肺结节的患者中有希望的效用。拟议的工作旨在澄清的机制，确定处置的F-18胆碱放射性示踪剂在正常和恶性组织，并比较三个领先的F-18标记的胆碱示踪剂候选人的生化特性：氟甲基胆碱（FCH），氟乙基胆碱（FECH），和氟甲基烯丙基胆碱（FMAC）。这项工作应提供一个更强的基础，解释PET成像研究的癌症放射性标记胆碱类似物，并提供有用的数据，为选择最佳的放射性示踪剂，进一步发展为临床成像剂。本研究有三个具体目的：1）通过体外实验和重组人CK酶的研究，探讨F-18标记胆碱类似物与C-14胆碱在9 L胶质瘤大鼠肿瘤和正常组织中的转运和代谢关系;（2）阐明荷9 L胶质瘤大鼠肿瘤摄取胆碱类似物与肿瘤灌注、胆碱转运的关系;和3）在两种炎症动物模型中评价F-18胆碱类似物与放射性标记的2-氟-2-脱氧葡萄糖（FDG）和胸苷的摄取。

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.