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

J Med Chem. 1997 Nov 21;40(24):3986-9. doi: 10.1021/jm970475+.

Abstract

The diethylenetriaminepentaacetic acid (DTPA) derivatives L-Bn-DTPA and D-Bn-DTPA were synthesized and radiolabeled with 111In3+. 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 predominantly 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anion Transport Proteins
  • Carrier Proteins / metabolism
  • Female
  • Glutathione Transferase / metabolism
  • Indium Radioisotopes / chemistry
  • Indium Radioisotopes / pharmacokinetics*
  • Isotope Labeling / methods
  • Kidney / metabolism
  • Liver / metabolism
  • Male
  • Pentetic Acid / analogs & derivatives*
  • Pentetic Acid / chemical synthesis
  • Pentetic Acid / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Rats, Wistar
  • Stereoisomerism
  • Tissue Distribution

Substances

  • Anion Transport Proteins
  • Carrier Proteins
  • Indium Radioisotopes
  • Radiopharmaceuticals
  • indium benzyldiethylenetriaminepentaacetic acid
  • Pentetic Acid
  • Glutathione Transferase