EFFECT OF STEREOCHEMISTRY ON THE CLEARANCE MECHANISM OF IN-111(III)-LABELED D-BENZYLDIETHYLENETRIAMINEPENTAACETIC OR L-BENZYLDIETHYLENETRIAMINEPENTAACETIC ACID

The diethylenetriaminepentaacetic acid (DTPA) derivatives L-Bn-DTPA an d D-Bn-DTPA were synthesized and radiolabeled with In-111(3+). The upt ake and clearance of the compounds were determined through biodistribu tion and excretion studies in Wistar rats. Both isomers readily cleare d from the animal. The D isomer showed relatively high kidney uptake a nd predominately renal clearance. The L isomer showed substantial kidn ey and liver uptake with equal biliary and renal clearance. Clearance was also evaluated in TR- Wistar rats, which are defective in the live r canalicular multispecific organic anion transporter (cMOAT) protein. cMOAT mediates hepatobiliary clearance of many organic anions. Both c ompounds were excreted through the urine in TR- Wistar rats, suggestin g that cMOAT is important in the clearance of the compounds from the l iver.