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: 2148344
• 负责人: NAGESWARA R PUTTAGUNTA
• 金额: $ 6.49万
• 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 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2148344
• 关键词: chemical synthesis; contrast media; gadolinium; laboratory mouse; laboratory rabbit; magnetic resonance imaging; method development

Magnetic resonance imaging (MRI) is a powerful tool for the diagnosis of a broad range of clinical conditions. Expensive contrast media (about $110.00/dose) contribute to its high cost. The goal of this SBIR grant is to perform the preliminary steps necessary for a pre-IND evaluation by the FDA of a new inexpensive agent, Gadolinium DTPA Bisglucosamide. Preliminary investigations show lower animal toxicity, improved gadolinium chelate stability and zinc transmetalation kinetics compared to several currently approved agents. It demonstrates a two-fold improvement in liver and renal enhancement compared with current extracellular MRI contrast agents. These attributes create significant potential for the commercialization of this agent. Magnetic Research, Inc. intends to: * Perfect and document the synthesis and purification of Gd DTPA bis- glucosamide. * Develop a source for bulk manufacture. * Perform pre-IND FDA documentation including minimum lethal dosage testing in animals. * Determine chemical properties (osmolality, viscosity, density). * Validate transmetalation kinetics and thermodynamic stabilities. * Perform shelf life stability and sterilization experiments. * Initiate the selection of human evaluation sites. Purification and analysis will be performed with high field NMR, supercritical flow chromatography, and high resolution CC-MS, and HPLC with fluorescence detection. Dr. Gary Booth, Brigham Young University, will perform animal minimum lethal dosage tests.

磁共振成像(MRI)是诊断本病的有力工具。 广泛的临床情况。昂贵的造影剂(约 110.00美元/剂)是其高成本的原因。这笔SBIR赠款的目标是 执行IND前评估所需的准备步骤 FDA推出了一种新的廉价试剂--DTPA双葡糖胺。 初步调查显示，动物毒性较低，Gd含量较高 几种络合物的稳定性和锌转位动力学的比较 当前批准的代理。它证明了肝脏的两倍改善。 与目前的细胞外MRI对比，肾脏增强 探员们。这些属性创造了巨大的潜力， 这种代理商的商业化。 磁力研究公司打算： *完善并记录Gd DTPA BIS的合成和纯化- 氨基葡萄糖。 *开发批量制造来源。 *执行IND前FDA文件，包括最低致死剂量 在动物身上进行试验。 *测定化学性质(渗透压、粘度、密度)。 *验证转金属动力学和热力学稳定性。 *进行保质期稳定性和灭菌试验。 *启动人类评估地点的选择。 提纯和分析将用高场核磁共振进行， 超临界流色谱、高分辨率CC-MS和高效液相色谱 用荧光检测。杨百翰大学加里·布斯博士， 将进行动物最小致死剂量测试。