Radiosynthesis and in vivo evaluation of [ 11C]MP-10 as a positron emission tomography radioligand for phosphodiesterase 10A

Christophe Plisson, Cristian Salinas, David Weinzimmer, David Labaree, Shu Fei Lin, Yu Shin Ding, Steen Jakobsen, Paul W. Smith, Kawanishi Eiji, Richard E. Carson, Roger N. Gunn, Eugenii A. Rabiner

研究成果: Contribution to journalArticle査読

40 被引用数 (Scopus)


Introduction: The aim of this study was to evaluate a newly reported positron emission tomography (PET) radioligand [ 11C]MP-10, a potent and selective inhibitor of the central phosphodiesterase 10A enzyme (PDE10A) in vivo, using PET. Methods: A procedure was developed for labeling MP-10 with carbon-11. [ 11C]MP-10 was evaluated in vivo both in the pig and baboon brain. Results: Alkylation of the corresponding desmethyl compound with [ 11C]methyl iodide produced [ 11C]MP-10 with good radiochemical yield and specific activity. PET studies in the pig showed that [ 11C]MP-10 rapidly entered the brain reaching peak tissue concentration at 1-2 min postadministration, followed by washout from the tissue. Administration of a selective PDE10A inhibitor reduced the binding in all brain regions to the levels of the cerebellum, demonstrating the saturability and selectivity of [ 11C]MP-10 binding. In the nonhuman primate, the brain tissue kinetics of [ 11C]MP-10 were slower, reaching peak tissue concentrations at 30-60 min postadministration. In both species, the observed rank order of regional brain signal was striatum>diencephalon>cortical regions=cerebellum, consistent with the known distribution and concentration of PDE10A. [ 11C]MP-10 brain kinetics were well described by a two-tissue compartment model, and estimates of total volume of distribution (V T) were obtained. Blocking studies with unlabeled MP-10 revealed the suitability of the cerebellum as a reference tissue and enabled the estimation of regional binding potential (BP ND) as the outcome measure of specific binding. Quantification of [ 11C]MP-10 binding using the simplified reference tissue model with cerebellar input function produced BP ND estimates consistent with those obtained by the two-tissue compartment model. Conclusion: We demonstrated that [ 11C]MP-10 possesses good characteristics for the in vivo quantification of the PDE10A in the brain by PET.

ジャーナルNuclear Medicine and Biology
出版ステータス出版済み - 8 2011

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 放射線学、核医学およびイメージング
  • 癌研究


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