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.
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.
