DEVELOPMENT OF GD DTPA BISGLUCOSAMIDE FOR MRI CONTRAST

磁共振成像（MRI）是一种安全而强大的诊断工具 适用于各种临床条件。便宜而有效的 磁性药物将在健康领域发挥越来越重要的作用 MRI护理管理钆DTPA双葡萄糖酰胺（Gd DTPA比加） 作为MRI造影剂具有很大的前景， 改进了肝脏、肾脏和高剂量成像的多功能性。 的目标 该SBIR赠款用于： (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)经济地大规模生产Gd DTPA比加。 (3)拜访并审核选定的合同制造工厂。 (4)配制并无菌填充0.5摩尔Gd DTPA比加，使用 I期开发的制剂数据。 (5)建立并验证IND所需的程序和方案 成绩. (6)进行急性毒性、亚慢性毒性、致突变性、 确定为必要的药代动力学和生物分布研究 I期IND申请。 (7)访问和稽查选定的合同毒理学机构。 (8)对Gd DTPA的体内去螯合作用进行详细研究 大鼠中比加与其他FDA批准的造影剂的关系。 (9)访问并选择I期和II期FDA临床研究的研究中心。 (10)与FDA一起审查IND要求，并提交IND。 拟议的商业应用：磁共振造影剂， 全球销售额超过10亿美元/年，构成了一个重要的 辅助MRI扫描。目前有四个代理商出售， 进入细胞外液间隙，占所有MRI造影剂的95（+）% 应用.每一个都是由一家外国公司拥有的。三个是FDA批准的， 在这个国家可用。UnivisionTM，钆DTPA双葡糖酰胺 由Magnetic Research公司开发的化合物，显示了可喜 比市场上已有的产品更有优势。

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.