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

doi:10.1016/j.bmc.2011.01.032

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

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54 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 language	English
Pages (from-to)	1666-1673
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	19
Issue number	5
DOIs	https://doi.org/10.1016/j.bmc.2011.01.032
State	Published - Mar 1 2011

Keywords

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

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10.1016/j.bmc.2011.01.032

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@article{4a1514d479c545e7b5ad39de68034c0d,

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-[ 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.",

keywords = "Carbon-11, Huntington's disease, MP-10, PDE10A, PET imaging",

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

note = "Funding Information: Financial support for these studies was provided by the National Institute of Health under 5R33MH081281-04 (RHM), NS058714, 1R21NS061025-01A2 and Intramural grant MIR-11-009 of Mallinckrodt Institute of Radiology in Washington University School of Medicine . The authors gratefully thank Christina M. Zukas, John Hood, Darryl Craig, Ruike Wang, Aixiao Li and Junfeng Li for their excellent technical assistance for the microPET studies in non-human primate. ",

year = "2011",

month = mar,

day = "1",

doi = "10.1016/j.bmc.2011.01.032",

language = "English",

volume = "19",

pages = "1666--1673",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

number = "5",

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TY - JOUR

T1 - Radiosynthesis and in vivo evaluation of [ 11C]MP-10 as a PET probe for imaging PDE10A in rodent and non-human primate brain

AU - Tu, Zhude

AU - Fan, Jinda

AU - Li, Shihong

AU - Jones, Lynne A.

AU - Cui, Jinquan

AU - Padakanti, Prashanth K.

AU - Xu, Jinbin

AU - Zeng, Dexing

AU - Shoghi, Kooresh I.

AU - Perlmutter, Joel S.

AU - MacH, Robert H.

N1 - Funding Information: Financial support for these studies was provided by the National Institute of Health under 5R33MH081281-04 (RHM), NS058714, 1R21NS061025-01A2 and Intramural grant MIR-11-009 of Mallinckrodt Institute of Radiology in Washington University School of Medicine . The authors gratefully thank Christina M. Zukas, John Hood, Darryl Craig, Ruike Wang, Aixiao Li and Junfeng Li for their excellent technical assistance for the microPET studies in non-human primate.

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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.

AB - 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.

KW - Carbon-11

KW - Huntington's disease

KW - MP-10

KW - PDE10A

KW - PET imaging

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DO - 10.1016/j.bmc.2011.01.032

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AN - SCOPUS:79952186381

SN - 0968-0896

VL - 19

SP - 1666

EP - 1673

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 5

ER -

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

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Keywords

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