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特殊能力。不幸的是，这种方法目前仅限于一种被批准的放射性药物18F-FDG，它可以测量肿瘤的新陈代谢。PET示踪剂的开发可以大大提高PET在肿瘤学中的潜力，这些示踪剂可以评估其他有用的临床参数，例如对肿瘤血流和缺氧的定量测量。这些信息对癌症的诊断和分期非常有用。我们建议开发一台微型62Znfl2Cu发生器，以在极高的等渗浓度下产生9.7分钟的62CuPET示踪剂，并进一步开发试剂盒配方，以提供62个铜-双(缩氨基硫脲)化合物的即时合成。第一阶段将集中展示用于两种灌注示踪剂的组合微型发生器和即刻试剂盒的可行性，这两种示踪剂分别是CuPTSM和x2CuETS，以及缺氧示踪剂62CuATSM。在第二阶段，将全面开发供人类使用的微型发生器和试剂盒配方，INDS将提交给FDA用于这三种化合物，最后将进行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低氧成像。由此得到的灌注标准化乏氧图有望产生高度优越的肿瘤局部乏氧测量，从而产生指导治疗的优越信息。可分发的发生器生产的示踪剂，加上PET的广泛可获得性，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.