A BASIC RESEARCH OF GADOLINIUM HYDROGEN A 4,7,10-TETRAAZACYCLODODECANE-1,4,7,10-TETRAACETATE WITH HIGH COMPLEX STABILITY AS A CONTRAST AGENT FOR MRI

Gadolinium hydrogen 4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (abbreviated Gd-DOTMA) was developed as a new contrast agent for magn etic resonance imaging. Our study focused on the evaluation of the pha rmaceutical properties as in vivo agent. The new modified process by w hich Gd-DOTMA was synthesized resulted in high yields of this agent. A high stability constant of 10(26) for Gd-DOTMA was determined at phys iological pH. It is more stable than Gd complex with tetraazacyclodode canetetraacetic acid (which is regarded as the most stable Gd complex) . The strong T1 relaxivities of 4.0 and 3.7 (mM.s)-1 at 0.5 tesla and 1.5 tesla were measured in the aqueous solution. The osmolarity of 0.5 M solution, dissolved with equal amounts of meglumine as a solubilize r is 1020 m Osmol/kg. This contrasting agent was studied in vivo by us ing rats as the experimental group. The agent showed strong enhancemen t of transplanted tumors within the rat population studied. This compo und is rapidly excreted by the kidneys, and has a half-life of 26 min in blood. The median lethal dose (LD50 value) of the stable Gd-DOTMA h as a favorable tolerance of over 12.3 mmol/kg.