Effect of stereochemistry on the clearance mechanism of In-111(III)-labeled D- or L-benzyldiethylenetriaminepentaacetic acid

The diethylenetriaminepentaacetic acid (DTPA) derivatives L-Bn-DTPA and D-Bn-DTPA were synthesized and radiolabeled with In-111(3+). The uptake and clearance of the compounds were determined through biodistribution and excretion studies in Wistar rats. Both isomers readily cleared from the animal. The D isomer showed relatively high kidney uptake and predominately renal clearance. The L isomer showed substantial kidney and liver uptake with equal biliary and renal clearance. Clearance was also evaluated in TR- Wistar rats, which are defective in the liver canalicular multispecific organic anion transporter (cMOAT) protein. cMOAT mediates hepatobiliary clearance of many organic anions. Both compounds were excreted through the urine in TR- Wistar rats, suggesting that cMOAT is important in the clearance of the compounds from the liver.