title: Radiosynthesis and in vivo evaluation of [11C]MP-10 as a PET probe for imaging PDE10A in rodent and non-human primate brain.
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.
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA. tuz@mir.wustl.edu
authors.forename: Zhude
authors.initials: Z
authors.lastname: Tu
authors.forename: Jinda
authors.initials: J
authors.lastname: Fan
authors.forename: Shihong
authors.initials: S
authors.lastname: Li
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Jones
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cui
authors.forename: Prashanth K
authors.initials: PK
authors.lastname: Padakanti
authors.forename: Jinbin
authors.initials: J
authors.lastname: Xu
authors.forename: Dexing
authors.initials: D
authors.lastname: Zeng
authors.forename: Kooresh I
authors.initials: KI
authors.lastname: Shoghi
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D000882:Haplorhini; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: C545121:2-((4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy)methyl)quinoline; D011720:Pyrazoles; D011804:Quinolines; D019275:Radiopharmaceuticals