Radiosynthesis and in vivo evaluation of [11C]MP-10 as a PET probe for imaging PDE10A in rodent and non-human primate brain

Bioorg Med Chem. 2011 Mar 1;19(5):1666-73. doi: 10.1016/j.bmc.2011.01.032. Epub 2011 Jan 22.

Abstract

2-((4-(1-[(11)C]Methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-quinoline (MP-10), a specific PDE10A inhibitor (IC(50)=0.18 nM with 100-fold selectivity over other PDEs), was radiosynthesized by alkylation of the desmethyl precursor with [(11)C]CH(3)I, ∼45% yield, >92% radiochemical purity, >370 GBq/μmol specific activity at end of bombardment (EOB). Evaluation in Sprague-Dawley rats revealed that [(11)C]MP-10 had highest brain accumulation in the PDE10A enriched-striatum, the 30 min striatum: cerebellum ratio reached 6.55. MicroPET studies of [(11)C]MP-10 in monkeys displayed selective uptake in striatum. However, a radiolabeled metabolite capable of penetrating the blood-brain-barrier may limit the clinical utility of [(11)C]MP-10 as a PDE10A PET tracer.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier
  • Brain* / diagnostic imaging
  • Brain* / metabolism
  • Haplorhini
  • Male
  • Positron-Emission Tomography / methods
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Radiopharmaceuticals* / chemical synthesis
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution

Substances

  • 2-((4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy)methyl)quinoline
  • Pyrazoles
  • Quinolines
  • Radiopharmaceuticals