Production and use of Pb-203 for cancer therapy research

描述(由申请人提供)：铅-212(铅-212)标记的分子作为潜在的靶向放射治疗剂治疗转移性黑色素瘤的研究取得了有希望的结果。根据美国癌症协会的数据，今年美国约有6万人被诊断出患有黑色素瘤，其中8000人将死于这种疾病。为了使铅-212黑色素瘤治疗进入临床试验，它需要一种用于治疗计划和疾病分期的成像替代物。联邦食品和药物管理局建议开发铅-203作为成像伴侣，这是本申请的主题。为了为临床试验做准备，动物研究将证明铅-203成像同位素是治疗性铅-212标记的可行替代品。将进行动物实验以确定该制剂对肿瘤细胞的亲和力，并将评估其生物分布。此外，为了满足FDA对临床试验和批准的药物产品的要求，将开发一种生产铅-203的方法，以便生产出支持基于铅-212的疗法的同位素。在成功完成这一第二阶段SBIR后，AlphaMed将完成所需的临床前动物工作，以支持IND申请使用铅-203标记的[DOTA]-ReCCMSH作为其基于铅-212的黑色素瘤治疗的成像合作伙伴。为了支持其他基于铅-212的疗法，AlphaMed将其铅-203生产方法列为药物主文件，可在IND申请中参考。靶向放射治疗在临床前试验中被证明对治疗转移性黑色素瘤非常有效。转移性黑色素瘤是一种致命的皮肤癌，在美国每年夺走8000人的生命。为了进行临床试验，将使用与治疗药物相同元素的成像同位素进行治疗计划。这项赠款申请的成功完成将证明所建议的成像同位素是合适的，并建立了可接受的同位素生产工艺。

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.