Production and use of Pb-203 for cancer therapy research

描述（由申请人提供）：以铅-212 （Pb-212）标记的分子作为转移性黑色素瘤的潜在靶向放射治疗剂的研究取得了可喜的结果。根据美国癌症协会的数据，今年美国将有大约6万人被诊断出患有黑色素瘤，其中8000人将死于这种疾病。要使Pb-212黑色素瘤疗法进入临床试验阶段，就需要一种替代治疗方案和疾病分期的成像方法。联邦食品和药物管理局建议将Pb-203开发为成像伴侣，这是本申请的主题。为了准备临床试验，动物研究将证明Pb-203成像同位素是治疗性Pb-212标签的可行替代品。将进行动物研究以确定药物对肿瘤细胞的亲和力，并评估生物分布。此外，为了满足FDA对临床试验和批准药物的要求，将开发一种Pb-203生产方法，以便生产同位素以支持基于Pb-212的治疗。在成功完成这项II期SBIR后，AlphaMed将完成临床前动物实验，以支持使用Pb-203标记的[DOTA]-ReCCMSH作为其基于Pb-212的黑色素瘤治疗的成像合作伙伴的IND申请。为了支持其他基于Pb-212的疗法，AlphaMed将把其Pb-203的生产方法列为药物主文件（Drug Master File），供IND应用参考。靶向放疗在治疗转移性黑色素瘤的临床前试验中显示出非常有效的效果。转移性黑色素瘤是一种致命的皮肤癌，在美国每年夺去8000人的生命。为了进行临床试验，与治疗剂相同元素的成像同位素将用于治疗计划。这项拨款申请的成功完成将证明所建议的成像同位素是合适的，并建立了一个可接受的同位素生产过程。

DESCRIPTION (provided by applicant): Promising results are being obtained from studies of molecules labeled with Lead-212 (Pb-212) as potential targeted radiotherapeutic agent against metastatic melanoma. According to the American Cancer Society approximately 60,000 people in the US will be diagnosed with melanoma this year, and 8,000 will die from this disease. For Pb-212 melanoma therapy to proceed to clinical trials, it requires an imaging surrogate for treatment planning and disease staging. The Federal Food and Drug Administration recommended Pb-203 be developed as the imaging companion, the subject of this application. To prepare for clinical trials, animal studies will demonstrate that Pb-203 imaging isotope is a viable substitute for the therapeutic Pb-212 label. Animal studies will be performed to determine the agent's affinity for tumor cells, biodistribution will be assessed. Additionally to satisfy FDA requirements for clinical trials and approved drug product, a Pb-203 production method will be developed so that the isotope can be produced to support Pb-212 based therapies. After successful completion of this Phase II SBIR, AlphaMed will have completed the preclinical animal work needed to support an IND application for using Pb-203 labeled [DOTA]-ReCCMSH as the imaging partner for its Pb-212 based melanoma therapy. To support other Pb-212 based therapies, AlphaMed will have its Pb-203 production method listed as a Drug Master File, available to be referenced in IND applications. Targeted radiotherapy has shown to be very effective in preclinical tests in treating metastatic melanoma, a deadly form of skin cancer that takes 8,000 lives a year in the US. To proceed to clinical trials, an imaging isotope of the same element as the therapeutic will be used for treatment planning. Successful completion of this grant application will demonstrate the proposed imaging isotope is suitable and an acceptable isotope production process is established.