DEVELOPMENT OF GD DTPA BISGLUCOSAMIDE FOR MRI CONTRAST

用于 MRI 造影的 GD DTPA 双葡萄糖酰胺的开发

• 批准号: 2016839
• 负责人: NAGESWARA R PUTTAGUNTA
• 金额: $ 74.6万
• 依托单位: MAGNETIC RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2016839
• 关键词: CHO cells; chemical synthesis; contrast media; diethylenetriaminepentaacetate; dogs; drug design /synthesis /production; drug screening /evaluation; gadolinium; guinea pigs; histopathology; human tissue; laboratory rabbit; laboratory rat; magnetic resonance imaging; pharmacokinetics

Magnetic resonance imaging (MRI) is a safe and powerful diagnostic tool for a wide range of clinical conditions. Inexpensive and efficient magnetopharmaceuticals will play an increasingly important role in health care management with MRI. Gadolinium DTPA Bisglucosamide (Gd DTPA BIGA) has great promise as an MRI contrast agent with very low toxicity and improved versatility for liver, renal, and high dose imaging. The goal of this SBIR grant is to: (1) Optimize our lab synthetic methodologies developed in Phase I for large scale industrial production. (2) Economically produce Gd DTPA BIGA in large scale. (3) Visit and audit selected contract manufacturing facility. (4) Formulate and sterile fill Gd DTPA BIGA at 0.5 Molar using formulation data developed in Phase I. (5) Establish and validate required procedures and protocols for IND submission. (6) Conduct acute toxicity, sub-chronic toxicity, mutagenicity, pharmacokinetics and biodistribution studies identified as necessary for IND application in Phase I. (7) Visit and audit selected contract toxicology facility. (8) Carry out a detailed investigation of in vivo de-chelation of Gd DTPA BIGA in rats in relation to other FDA-approved contrast agents. (9) Visit and select sites for Phase I and Phase II FDA clinical studies. (10) Review IND requirements with the FDA, and submit an IND. PROPOSED COMMERCIAL APPLICATION: Magnetic resonance contrast media, with worldwide sales exceeding $1 billion/year, constitutes an important adjuvant to MRI scanning. Currently four agents are sold which distribute into the extracellular fluid space and comprise 95(+)% of all MRI contrast applications. Each is owned by a foreign firm. Three are FDA-approved and available in this country. UnivisionTM, the Gadolinium DTPA Bisglucosamide compound being developed by Magnetic Research, Inc., shows promising advantages over those already on the market.

磁共振成像 (MRI) 是一种安全且强大的诊断工具 适用于各种临床情况。廉价高效 磁性药物将在健康领域发挥越来越重要的作用 通过 MRI 进行护理管理。钆 DTPA 双葡萄糖酰胺 (Gd DTPA BIGA) 作为 MRI 造影剂具有极低的毒性和良好的前景 改进了肝脏、肾脏和高剂量成像的多功能性。 目标是 这笔 SBIR 赠款旨在： (1) 优化我们在第一阶段开发的实验室合成方法 大规模工业生产。 (2)经济规模化生产Gd DTPA BIGA。 (3) 参观并审核选定的合同制造工厂。 (4) 使用 0.5 摩尔浓度的 Gd DTPA BIGA 配制并无菌填充 第一阶段开发的配方数据。 (5) 建立并验证 IND 所需的程序和协议 提交。 (6) 具有急性毒性、亚慢性毒性、致突变性、 药代动力学和生物分布研究被认为是必要的 一期IND申请。 (7) 参观并审核选定的合同毒理学设施。 (8) 对Gd DTPA体内脱螯合进行详细研究 BIGA 在大鼠中与 FDA 批准的其他造影剂的关系。 （9）考察并选择FDA I期和II期临床研究地点。 (10) 与 FDA 审查 IND 要求，并提交 IND。 拟议的商业应用：磁共振造影剂，具有 全球销售额每年超过 10 亿美元，构成了重要的 MRI 扫描的辅助。目前已售出四位代理商，负责分销 进入细胞外液空间并占所有 MRI 对比的 95(+)% 应用程序。每一个都由一家外国公司拥有。其中三个已获得 FDA 批准 在这个国家可用。 UnivisionTM，钆 DTPA 双葡萄糖酰胺 Magnetic Research, Inc. 正在开发的化合物显示出良好的前景 与市场上现有产品相比的优势。