Instant Kit Synthesis of 62Cu Radiopharmaceuticals

描述（由申请人提供）： 正电子发射断层扫描（PET）是一种快速发展的非侵入性成像技术，具有提供定量功能信息的卓越能力。不幸的是，这种方式目前仅限于单一批准的放射性药物18F-FDG，其测量肿瘤代谢。PET在肿瘤学中的潜力可以通过开发PET示踪剂来大大提高，PET示踪剂可以评估其他有用的临床参数，例如肿瘤灌注和缺氧的定量测量。这些信息对于癌症的诊断和分期非常有用。我们建议开发微型62 Znf 12 Cu发生器以在非常高的等渗浓度下产生9.7分钟的62 Cu PET示踪剂，并进一步开发试剂盒制剂以提供62 Cu-双（缩氨基硫脲）化合物的即时合成。第一阶段将集中于证明组合的微型发生器和即时试剂盒用于两种灌注示踪剂（约Cu-PTSM和x2 CU-ETS）和缺氧示踪剂62 Cu-ATSM的可行性。在第二阶段，微型发电机和试剂盒配方将完全开发用于人类使用，IND将提交给FDA的三种化合物，最后，有限的临床可行性研究，重点是在简短的成像会议中完成的连续灌注和缺氧成像。期望得到的灌注标准化缺氧图产生高度上级的局部肿瘤缺氧测量，从而产生指导治疗的上级信息。可分配的发生器产生的示踪剂，加上PET的广泛扩展的可用性，可以在癌症患者的治疗和管理中产生深远的好处。

DESCRIPTION (provided by applicant): Positron Emission Tomography (PET) is a rapidly emerging non-invasive imaging technique with the exceptional ability to provide quantitative functional information. Unfortunately, this modality is currently limited to a single approved radiopharmaceutical agent, 18F-FDG, which measures tumor metabolism. The potential of PET in oncology can be advanced substantially by development of PET tracers that can assess other useful clinical parameters, such as the quantitative measurement of tumor perfusion and hypoxia. Such information is extremely useful for diagnosis and staging of cancer. We propose to develop a micro 62Znfl2Cu generator to produce the 9.7 minute 62Cu PET tracer at very high isotonic concentration and further to develop kit formulations to provide instant synthesis of 62 Cu-bis(thiosemicarbazone) compounds. Phase I will concentrate on demonstrating the feasibility of the combined microgenerator and instant kits for the two perfusion tracers approximately Cu-PTSM and x2CU-ETS, and the hypoxia tracer 62 Cu-ATSM. In Phase II, the microgenerator and kit formulations will be fully developed for human use, INDs will be submitted to the FDA for the three compounds, and finally, limited clinical feasibility studies focusing on serial perfusion and hypoxia imaging completed in a brief imaging session will be performed. The resulting perfusion normalized hypoxia map is expected to produce a highly superior measure of regional tumor hypoxia and thus superior information to guide treatment. The distributable generator produced tracers, together with the widely expanding availability of PET, can have far-reaching benefits in cancer patient treatment and management.