A Pb-212 Generator Using Resistant Substrate and Rn Cold Trapping

描述(由申请人提供)：在临床前动物试验中，靶向的铅-212疗法在接受这种疗法的最高剂量组中显示出一种治愈。将动物研究中最有效的剂量扩大到人类身上，人类所需的剂量将从50微克/平方英寸增加到100微克/平方英寸。这个应用程序将研究一种方法，该方法将提供支持这些需求的生成器系统。这项拟议的工作将研究一种发电机系统，该系统将捕获短暂的氡-220，并分离和测试所获得的铅-212/铋-212。Ra-224和Th-228发射发生器将扩大到多毫升水平，并随着时间的推移评估其性能，包括总当量和验证Ra-224或Th-228的零突破。最后，将测试产品铅-212/铋-212标记抗黑色素瘤多肽部分的适合性，以及预期发射发生器所预期的铅-212的改进的比活性。 公共卫生相关性：黑色素瘤是一种致命的皮肤癌，临床前动物试验已经证明，使用铅-212标记的多肽可以治愈黑色素瘤。随着这种疗法进入临床，目前的发电机系统需要改进，以适应预期的更高剂量水平。

DESCRIPTION (provided by applicant): Targeted Pb-212 therapy in preclinical animal tests has shown a cure in groups receiving the highest dose of this therapy. Scaling the dose that was most efficacious in animal studies to people would bring the human dose required from 50 to 100 mCi. This application will research an approach that would provide a generator system that would support these requirements. The proposed work will investigate a generator system that would trap the short-lived radon-220 and isolate and test Pb-212/Bi-212 obtained. The Ra-224 and Th-228 emanation generators would be scaled up to the multi-millicurie level and assessment of their performance over time, including overall yield and verification of zero breakthrough of Ra-224 or Th-228. Finally, the suitability of the product Pb-212/Bi-212 to label anti- melanoma peptide moieties and the improved specific activity of Pb-212 expected of an emanation generator will be tested. PUBLIC HEALTH RELEVANCE: A cure for melanoma, a deadly form of skin cancer, has been demonstrated in preclinical animal tests using Pb-212 labeled peptide. As this therapy moves to the clinic the current generator system needs to be improved to accommodate higher dose levels that are anticipated to be administered.