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

Zhude Tu, Jinda Fan, Shihong Li, Lynne A. Jones, Jinquan Cui, Prashanth K. Padakanti, Jinbin Xu, Dexing Zeng, Kooresh I. Shoghi, Joel S. Perlmutter, Robert H. MacH

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

2-((4-(1-[ 11C]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 [ 11C]CH 3I, ∼45% yield, >92% radiochemical purity, >370 GBq/μmol specific activity at end of bombardment (EOB). Evaluation in Sprague-Dawley rats revealed that [ 11C]MP-10 had highest brain accumulation in the PDE10A enriched-striatum, the 30 min striatum: cerebellum ratio reached 6.55. MicroPET studies of [ 11C]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 [ 11C]MP-10 as a PDE10A PET tracer.

Original languageEnglish (US)
Pages (from-to)1666-1673
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number5
DOIs
StatePublished - Mar 1 2011

Keywords

  • Carbon-11
  • Huntington's disease
  • MP-10
  • PDE10A
  • PET imaging

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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