Production and use of Pb-203 for cancer therapy research

Pb-203 的生产和用于癌症治疗研究的用途

• 批准号: 7394867
• 负责人: HERBERT A MOORE
• 金额: $ 39.76万
• 依托单位: ALPHAMED, INC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7394867
• 关键词: 90Y; Academic Medical Centers; Acute; Affinity; American Cancer Society; Animals; Applications Grants; Avidity; Award; Behavior; Biodistribution; Clinical Trials; Colon Carcinoma; Companions; Conduct Clinical Trials; Development; Diagnosis; Diagnostic; Diagnostic Imaging; Disease; Doctor of Medicine; Documentation; Dose; Drug Formulations; Drug Kinetics; Elements; Extramural Activities; Failure; Family suidae; Funding; Grant; I131 isotope; Image; Indium-111; Inorganic Chemistry; Iodine I 131 Metaiodobenzylguanidine; Isotopes; Label; Laboratories; Letters; Life; Malignant Neoplasms; Malignant neoplasm of thyroid; Metastatic Melanoma; Methods; Missouri; Monitor; Mus; Numbers; Octreotide; Ovarian; Pacific Northwest; Pancreas; Patients; Peptides; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Photons; Preclinical Testing; Process; Production; Radiation; Radiation therapy; Radioisotopes; Radiolabeled; Radium-224; Recycling; Research; Research Institute; Rodent; Skin Cancer; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Somatostatin Receptor; Source; Staging; Targeted Radiotherapy; Thallium; Therapeutic; Therapeutic Agents; Therapeutic Studies; Thyroid carcinoma; Time; Tissues; Toxic effect; United States Food and Drug Administration; United States National Institutes of Health; Universities; Work; base; bioimaging; cancer therapy; dosimetry; follow-up; intraperitoneal; melanoma; milligram; neoplastic cell; oncology; pre-clinical; preclinical study; professor; programs; radiotracer; treatment planning; tumor; uptake

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.

描述（由申请人提供）：对 Lead-212 (Pb-212) 标记的分子作为针对转移性黑色素瘤的潜在靶向放射治疗剂的研究获得了有希望的结果。据美国癌​​症协会称，今年美国将有大约 60,000 人被诊断出患有黑色素瘤，8,000 人将死于这种疾病。 Pb-212 黑色素瘤治疗要进入临床试验，需要影像学替代物来制定治疗计划和疾病分期。美国联邦食品和药物管理局建议将 Pb-203 开发为成像伴侣，即本申请的主题。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 标记的可行替代品。将进行动物研究以确定该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品的要求，还将开发 Pb-203 生产方法，以便生产同位素来支持基于 Pb-212 的疗法。成功完成 II 期 SBIR 后，AlphaMed 将完成支持 IND 申请所需的临床前动物工作，以使用 Pb-203 标记的 [DOTA]-ReCCMSH 作为其基于 Pb-212 的黑色素瘤治疗的成像伙伴。为了支持其他基于 Pb-212 的疗法，AlphaMed 将其 Pb-203 生产方法列为药物主文件，可供 IND 申请中参考。在治疗转移性黑色素瘤的临床前测试中，靶向放疗已被证明非常有效。转移性黑色素瘤是一种致命的皮肤癌，在美国每年夺去 8,000 人的生命。为了进行临床试验，将使用与治疗剂相同元素的成像同位素来制定治疗计划。成功完成这项拨款申请将证明所提议的成像同位素是合适的，并且建立了可接受的同位素生产工艺。