(R)- and (S)-[11C]verapamil as PET-tracers for measuring P-glycoprotein function: in vitro and in vivo evaluation

Nucl Med Biol. 2003 Oct;30(7):747-51. doi: 10.1016/s0969-8051(03)00078-7.


The mdr1 gene product P-glycoprotein (P-gp) is involved in the bioavailability and pharmacokinetics of various drugs. Racemic [(11)C]verapamil has been used to image P-gp expression in vivo. A racemic tracer, however, is not suitable for quantification. The purpose of the present study was to identify the most appropriate enantiomer of [(11)C]verapamil as a potential PET-tracer for quantifying P-gp function. The two enantiomers, (R)- and (S)-[(11)C]verapamil, were synthesized and studied in vivo. For the in vivo model mdr1a/1b double gene knock-out and wild type mice were used. The in vitro study made use of the LLC-PK1 MDR cell line to examine the P-gp mediated transport of both enantiomers. The biodistribution of (R)- and (S)-[(11)C]verapamil in dKO and WT mice demonstrated no stereoselectivity of verapamil for P-gp in the blood-brain barrier and in the testes. In addition, no significant differences in P-gp transport for both enantiomers were observed in the in vitro experiments. Previous studies have shown that (R)-verapamil is metabolized less in man and that it has lower affinity for calcium channels. Since (R)- and (S)-verapamil have equal transport for P-gp, the (R)-enantiomer seems to be the best and safest candidate as PET-tracer for measuring P-gp function in vivo.

Publication types

  • Comparative Study
  • Evaluation Study
  • Validation Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Alcohol Oxidoreductases
  • Animals
  • Blood-Brain Barrier / diagnostic imaging*
  • Blood-Brain Barrier / metabolism*
  • Carbon Radioisotopes / blood
  • Carbon Radioisotopes / pharmacokinetics*
  • Isomerism
  • Ketol-Acid Reductoisomerase
  • LLC-PK1 Cells
  • Metabolic Clearance Rate
  • Mice
  • Mice, Knockout
  • Organ Specificity
  • Protein Transport / physiology
  • Radiopharmaceuticals / blood
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Swine
  • Tissue Distribution
  • Tomography, Emission-Computed / methods*
  • Verapamil / blood
  • Verapamil / pharmacokinetics*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Carbon Radioisotopes
  • Radiopharmaceuticals
  • Verapamil
  • Alcohol Oxidoreductases
  • Ketol-Acid Reductoisomerase