Hepato-biliary and renal excretion in mice of charged and neutral gadolinium complexes of cyclic tetra-aza-phosphinic and carboxylic acids.

Tissue distribution of 21 new 157/153Gd complexes was measured at 5 min and 24 hr after an intravenous injection into mice. A complex was judged to be stable in vivo when the percentage of 153Gd retained in the liver and skeleton at 24 hr was comparable with that of 153Gd(DOTA)-. Complexes varied in net charge and lipophilicity and 20 were phosphinic or carboxylic acid derivatives of tetra-aza-cyclo-dodecane. Three anionic, lipophilic complexes were cleared predominantly by the hepato-biliary pathway and were stable in vivo. The remaining 18 complexes were cleared mainly by the kidneys. Of these 18, 1 anionic, 8 neutral, and 3 cationic complexes were stable in vivo. These findings augur well for the future of hepato-biliary and general purpose Gd contrast enhancing agents for MRI.