DEVELOPMENT OF GD DTPA BISGLUCOSAMIDE FOR MRI CONTRAST

磁共振成像（MRI）是诊断 广泛的临床条件。昂贵的造影剂（约 110.00美元/剂）导致其成本高。该SBIR赠款的目标是 执行IND前评价所需的初步步骤， FDA批准了一种新的廉价药物，钆DTPA双葡萄糖酰胺。 初步调查显示，较低的动物毒性，改善钆 螯合物稳定性和锌金属转移动力学 目前已批准的代理商。它证明了肝脏的两倍改善 与目前的细胞外MRI造影剂相比， 剂.这些属性为 该代理商的商业化。 Magnetic Research，Inc.打算： * 完善并记录Gd DTPA双- 葡萄糖酰胺。 * 开发批量生产的来源。 * 执行IND前FDA文件，包括最小致死剂量 在动物身上做试验。 * 测定化学性质（渗透压、粘度、密度）。 * 金属转移动力学和热力学稳定性。 * 进行有效期稳定性和灭菌实验。 * 启动人体评价部位的选择。 将用高场NMR进行纯化和分析， 超临界流动色谱、高分辨率CC-MS和HPLC 荧光检测。杨百翰大学的加里·布斯博士 将进行动物最小致死剂量试验

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.