Developing Nanodosing of Iobenguane I 131 for Radiotherapy

开发用于放射治疗的 Iobenguane I 131 纳米剂量

• 批准号: 7218903
• 负责人: James F Kronauge
• 金额: $ 57.39万
• 依托单位: MOLECULAR INSIGHT PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7218903
• 关键词: iodine; neoplasm /cancer; performance; polymers; radiotracer

DESCRIPTION (provided by applicant): This Phase 2 SBIR is for the development of a drug product identified and demonstrated in the Phase 1 SBIR award (R43CA15120-01). The ultimate goal is to produce, sell and deliver doses of high specific activity iobenguane I 131 for radiotherapy in adults and children with neuroendocrine tumors. These are rare tumors with only about 800 cases a year in the US but with poor outcome and no approved effective treatment. The innovation in this proposal is that it uses a solid phase synthetic process to make a proven diagnostic agent in a radio-therapeutic quantity (1 Curie) without the pharmacologically active carrier compound. A type B pre-IND development was held with the FDA where they definitively stated that USP test methods are insufficient to permit human testing of iobenguane I 131 produced by a new method. However, the FDA concluded that literature reports indicate iobenguane I 131 therapy is efficient for treating neuroendocrine tumors and granted Orphan Drug and Fast Tract status for the development of high specific activity drug product. To meet the required quality control of components of the chemistry, manufacturing and controls component of a IND application, the polymer supported drug precursor will be produced according to current good manufacturing practices and analytical tests developed and validated to confirm the identity, purity, performance and impurity profile of the critical component drug precursor. We will also develop a Drug Master File and execute batch records for the production process of the radioactive drug substance. Finally batches of the final drug product will be made and tested for stability and bio-equivalence in transporter expressing cells and in animals.

描述(由申请人提供)：该第二阶段SBIR用于开发第一阶段SBIR奖(R43CA15120-01)中确定和展示的药物产品。最终目标是生产、销售和提供剂量高比活度的碘-131，用于成人和儿童神经内分泌肿瘤的放射治疗。这是一种罕见的肿瘤，在美国每年只有大约800例，但结果很差，也没有得到批准的有效治疗方法。该方案的创新之处在于，它使用固相合成工艺来制造经过验证的放射治疗量(1居里)的诊断剂，而不使用具有药理活性的载体化合物。与FDA一起进行了B型前IND开发，他们明确表示，USP测试方法不足以允许对由新方法生产的Iobenguane I 131进行人体测试。然而，FDA得出的结论是，文献报告表明，Iobenguane I 131疗法对于治疗神经内分泌肿瘤是有效的，并被授予孤儿药物和快速通道地位，用于开发高比活性药物产品。为了满足IND应用的化学、制造和控制组件所需的质量控制，聚合物支持的药物前体将根据当前良好的制造实践和开发和验证的分析测试来生产，以确认关键成分药物前体的身份、纯度、性能和杂质分布。我们还将制定药品总档案，并对放射性药物的生产过程执行批次记录。最后，将生产一批最终药物产品，并在表达转运蛋白的细胞和动物中测试其稳定性和生物等效性。