Development of GD DTPA Bisglucosamide for MRI Contrast

Magnetic resonance imaging (MRI) is a powerful tool for the diagnosis of a broad range of clinicalconditions. Expensive contrast media (about $110.00/dose) contribute to its high cost. We will performthe 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, improvedgadolinium chelate stability and zinc transmetalation kinetics compared to several currently approvedagents. It demonstrates a two-fold improvement in liver and renal enhancement compared with currentextracellular MRI contrast agents. These attributes create significant potential for the commercializationof this agent. We intend to * perfect and document the synthesis and purification of Gd DTPAbis-glucosamide. *Develop a source for bulk manufacture. * Perform pre-IND FDA documentationincluding minimum lethal dosage testing in animals. * Determine chemical properties (osmolality,viscosity, density). * Validate transmetalation kinetics and thermodynamic stabilities. * Perform shelflife stability and sterilization experiments. * Initiate the selection of human evaluation sites. Purificationand analysis will be performed with high field NMR, supercritical flow chromatography, and highresolution CC-MS, and HPLC with fluorescence detection.