TY - JOUR
T1 - Radiosynthesis and in vivo evaluation of [ 11C]MP-10 as a positron emission tomography radioligand for phosphodiesterase 10A
AU - Plisson, Christophe
AU - Salinas, Cristian
AU - Weinzimmer, David
AU - Labaree, David
AU - Lin, Shu Fei
AU - Ding, Yu Shin
AU - Jakobsen, Steen
AU - Smith, Paul W.
AU - Eiji, Kawanishi
AU - Carson, Richard E.
AU - Gunn, Roger N.
AU - Rabiner, Eugenii A.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.nucmedbio.2011.02.005
DO - 10.1016/j.nucmedbio.2011.02.005
M3 - Article
C2 - 21843784
AN - SCOPUS:80051693428
SN - 0969-8051
VL - 38
SP - 875
EP - 884
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 6
ER -
