11C TOPOTECAN PET IMAGING

11C 拓扑替康 PET 成像

• 批准号: 7378046
• 负责人: RAYMOND F MUZIC
• 金额: $ 0.27万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378046
• 关键词: 11C; TOPOTECAN; PET; IMAGING

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Topotecan, a topoisomerase I inhibitor, is a drug made by Glaxo Smith Kline and sold as Hycamtin for treatment of patients with metastatic carcinoma of the ovary and small cell lung cancer (SCLC) after failure of initial or subsequent chemotherapy. Our long term goals are to optimize the dosing strategy of topotecan to achieve maximal efficacy and to identify, at the earliest time point possible, whether or not a particular patient will likely benefit from topotecan treatment. PET scan is proposed for this purpose. This study is intended to firstly demonstrate proof-of-principle that tumor uptake of topotecan can be measured in humans noninvasively with PET and secondly to provide evidence that PET-measured uptake has potential to be an early predictor of response to therapy. Topotecan blocks cell proliferation by blocking DNA replication. We intend to label topotecan with 11-C to create [11-C]topotecan, and to image its in vivo distribution in humans. Notably, this is the same molecule as the topotecan drug--the only difference is that an 11-C atom replaces a non-radioactive C atom. The objectives of this study are to: 1) label topotecan with 11-C 2) determine whether or not tumor uptake of [11-C]topotecan occurs quickly enough and at sufficient concentration to be measured immediately following a bolus of a tracer quantity 3) obtain preliminary indication of whether or not [11-C]topotecan imaging has potential to be an early predictor of response to topotecan therapy. A method to directly and noninvasively assess delivery of drug to tumors in humans has numerous applications. The potential of PET to determine quantitatively the levels of accumulation of chemotherapeutic agents in tumor offers the prospect of patient-specific dosing. We expect that PET-measured uptake of topotecan will be an early predictor of response to this therapy. It is already known that response rate is greater in patients with higher plasma levels of topotecan in lactone form. It may be that plasma levels serve as a surrogate to tumor drug accumulation and that direct measurement of drug concentration in tumor would be a better predictor of response than concentration in plasma. Subjects must have histologically documented ovarian carcinoma, small cell lung cancer, or other cancer with brain metastases that make the subject a candidate for topotecan therapy based on their primary oncologist's clinical decision. 10 subjects will be enrolled.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。拓扑替康（Topotecan）是一种拓扑异构酶 I 抑制剂，是由葛兰素史克生产的药物，以 Hycamtin 销售，用于治疗初始或后续化疗失败后的卵巢转移癌和小细胞肺癌 (SCLC) 患者。我们的长期目标是优化拓扑替康的给药策略，以实现最大疗效，并尽早确定特定患者是否可能从拓扑替康治疗中受益。 PET 扫描就是为此目的而提出的。这项研究的目的首先是证明原理证明，即可以使用 PET 无创地测量人体肿瘤对托泊替康的摄取，其次提供证据，证明 PET 测量的摄取有可能成为治疗反应的早期预测因子。拓扑替康通过阻断 DNA 复制来阻断细胞增殖。我们打算用 11-C 标记托泊替康以创建 [11-C]托泊替康，并对其在人体中的体内分布进行成像。值得注意的是，这与拓扑替康药物是相同的分子——唯一的区别是 11-C 原子取代了非放射性 C 原子。本研究的目的是： 1) 用 11-C 标记托泊替康 2) 确定肿瘤对 [11-C]托泊替康的摄取是否足够快且浓度足够，以便在推注示踪剂后立即进行测量 3 ）获得 [11-C]托泊替康成像是否有可能成为托泊替康治疗反应的早期预测因子的初步指示。直接且无创地评估药物向人体肿瘤的输送的方法具有广泛的应用。 PET 定量确定肿瘤中化疗药物累积水平的潜力为患者特异性给药提供了前景。我们预计 PET 测量的托泊替康摄取量将成为对该疗法反应的早期预测指标。众所周知，内酯形式拓扑替康血浆水平较高的患者的缓解率较高。血浆水平可能可以作为肿瘤药物蓄积的替代指标，并且直接测量肿瘤中的药物浓度比血浆中的药物浓度更能预测反应。受试者必须患有组织学记录的卵巢癌、小细胞肺癌或其他具有脑转移的癌症，使得受试者根据其主要肿瘤科医生的临床决定成为拓扑替康治疗的候选者。将招收10个科目。