Choline Tracers for Imaging of Cancer

用于癌症成像的胆碱示踪剂

• 批准号: 7556583
• 负责人: Timothy R. DeGrado
• 金额: $ 7.58万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 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 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7556583
• 关键词: Animal Model; Bacillus (bacterium); Benign; Betaine; Biochemical; Biodistribution; Blood; Blood flow; Bolus Infusion; Brain Neoplasms; C14 isotope; Cancer Model; Cell Respiration; Chemicals; Choline; Choline Kinase; Chronic; Clinical; Collagen Arthritis; Cyclotrons; Data; Deoxyglucose; Deposition; Detection; Development; Diagnostic; Diagnostic Imaging; Diagnostic Neoplasm Staging; Enzymes; Esophageal carcinoma; Evaluation; Exhibits; Functional Imaging; Glioma; Glucose; Goals; Half-Life; High Pressure Liquid Chromatography; Human; Image; Imaging Techniques; In Vitro; Inflammation; Inflammatory; Kidney; Kinetics; Label; Laboratories; Liver neoplasms; Lung nodule; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Mediating; Metabolic; Metabolism; Metastatic Prostate Cancer; Modeling; Neoplasms; Normal tissue morphology; Organic Cation Transporter; Pathology; Patients; Pattern; Perfusion; Phosphorylation; Physiological Processes; Positron; Positron-Emission Tomography; Process; Production; Property; Prostate; Radiolabeled; Rain; Rattus; Recombinants; Relative (related person); Research; Research Personnel; Role; Site; Specificity; Techniques; Thymidine; Time; Tissue Viability; Tissues; Tracer; Urine; Work; Xenograft procedure; analog; base; cancer cell; cancer imaging; choline analog; choline transporter; fluoroethylcholine; in vivo; intravenous administration; malignant breast neoplasm; metastatic esophageal; neoplastic cell; novel; programs; pulmonary granuloma; radiotracer; research study; tissue processing; tumor; uptake

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。

项目成果

Synthesis and biodistribution of new radiolabeled high-affinity choline transporter inhibitors [11C]hemicholinium-3 and [18F]hemicholinium-3.

新型放射性标记高亲和力胆碱转运蛋白抑制剂[11C]hemicholinium-3和[18F]hemicholinium-3的合成和生物分布。

• 发表时间: 2007-04-15
• 影响因子: 2.7
• 作者: Zheng, Qi;Gao, Mingzhang;Mock, Bruce H;Wang, Shuyan;Hara, Toshihiko;Nazih, Rachid;Miller, Michael A;Receveur, Tim J;Lopshire, John C;Groh, William J;Zipes, Douglas P;Hutchins, Gary D;DeGrado, Timothy R
• 通讯作者: DeGrado, Timothy R

Cancer imaging with fluorine-18-labeled choline derivatives.

使用氟 18 标记的胆碱衍生物进行癌症成像。

• 发表时间: 2007-11
• 影响因子: 4.9
• 作者: Kwee, Sandi A;DeGrado, Timothy R;Talbot, Jean Noel;Gutman, Fabrice;Coel, Marc N
• 通讯作者: Coel, Marc N

Synthesis and evaluation of near-infrared (NIR) dye-herceptin conjugates as photoacoustic computed tomography (PCT) probes for HER2 expression in breast cancer.

近红外 (NIR) 染料-赫赛汀缀合物作为乳腺癌 HER2 表达的光声计算机断层扫描 (PCT) 探针的合成和评估。

• DOI: 10.1021/bc700482u
• 发表时间: 2008-05-28
• 期刊: Bioconjugate chemistry
• 影响因子: 4.7
• 作者: Sibaprasad Bhattacharyya;Shuyan Wang;D. Reinecke;W. Kiser;R. Kruger;T. DeGrado
• 通讯作者: T. DeGrado

Choline phosphorylation and regulation of transcription of choline kinase α in hypoxia.

缺氧时胆碱磷酸化和胆碱激酶α转录的调节。

• 发表时间: 2012-01
• 影响因子: 6.5
• 作者: Bansal, Aditya;Harris, Robert A;DeGrado, Timothy R
• 通讯作者: DeGrado, Timothy R

Noninvasive evaluation of fat-carbohydrate metabolic switching in heart and contracting skeletal muscle.

心脏和收缩骨骼肌中脂肪-碳水化合物代谢转换的无创评估。

• 发表时间: 2019
• 作者: DeGrado, Timothy R;Pandey, Mukesh K;Belanger, Anthony P;Basuli, Falguni;Bansal, Aditya;Wang, Shuyan
• 通讯作者: Wang, Shuyan