5-(5-(6-[11C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin- 2-yl)-1H-indole as a potential PET radioligand for imaging cerebral α7-nAChR in mice

Yongjun Gao; Hayden T Ravert; Heather Valentine; Ursula Scheffel; Paige Finley; Dean Foster Wong; Robert F. Dannals; Andrew G. Horti

doi:10.1016/j.bmc.2012.04.056

5-(5-(6-[¹¹C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin- 2-yl)-1H-indole as a potential PET radioligand for imaging cerebral α7-nAChR in mice

Yongjun Gao, Hayden T Ravert, Heather Valentine, Ursula Scheffel, Paige Finley, Dean Foster Wong, Robert F. Dannals, Andrew G. Horti

School of Medicine

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

The radiosynthesis and in vivo evaluation of 5-(5-(6-[¹¹C] methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [ ¹¹C]rac-(1), a potential PET tracer for α7 nicotinic acetylcholine receptors (α7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation of 7 with [ ¹¹C]CH₃I afforded [¹¹C]rac-1 in an average radiochemical yield of 30 ± 5% (n = 5) with high radiochemical purity and an average specific radioactivity of 444 ± 74 GBq/μmol (n = 5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [¹¹C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal α7-nAChRs.

Original language	English (US)
Pages (from-to)	3698-3702
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	12
DOIs	https://doi.org/10.1016/j.bmc.2012.04.056
State	Published - Jun 15 2012

Keywords

Nicotinic acetylcholine receptors
Positron emission tomography
Radioligand
α7-nAChR

ASJC Scopus subject areas

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

Access to Document

10.1016/j.bmc.2012.04.056

Cite this

@article{ca732b9f7d534b23b3ca7456449cbea6,

title = "5-(5-(6-[11C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin- 2-yl)-1H-indole as a potential PET radioligand for imaging cerebral α7-nAChR in mice",

abstract = "The radiosynthesis and in vivo evaluation of 5-(5-(6-[11C] methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [ 11C]rac-(1), a potential PET tracer for α7 nicotinic acetylcholine receptors (α7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation of 7 with [ 11C]CH3I afforded [11C]rac-1 in an average radiochemical yield of 30 ± 5% (n = 5) with high radiochemical purity and an average specific radioactivity of 444 ± 74 GBq/μmol (n = 5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [11C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal α7-nAChRs.",

keywords = "Nicotinic acetylcholine receptors, Positron emission tomography, Radioligand, α7-nAChR",

author = "Yongjun Gao and Ravert, {Hayden T} and Heather Valentine and Ursula Scheffel and Paige Finley and Wong, {Dean Foster} and Dannals, {Robert F.} and Horti, {Andrew G.}",

note = "Funding Information: The authors would like to thank Dr. William H. Bunnelle (Abbott Laboratories) for helpful discussions and Mrs. Judy Buchanan for editorial assistance. This research was supported in part by the Division of Nuclear Medicine of Johns Hopkins University School of Medicine and by NIH Grants DA020777 and MH079017 (A.H.). ",

year = "2012",

month = jun,

day = "15",

doi = "10.1016/j.bmc.2012.04.056",

language = "English (US)",

volume = "20",

pages = "3698--3702",

journal = "Bioorganic and Medicinal Chemistry",

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publisher = "Elsevier Limited",

number = "12",

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T1 - 5-(5-(6-[11C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin- 2-yl)-1H-indole as a potential PET radioligand for imaging cerebral α7-nAChR in mice

AU - Gao, Yongjun

AU - Ravert, Hayden T

AU - Valentine, Heather

AU - Scheffel, Ursula

AU - Finley, Paige

AU - Wong, Dean Foster

AU - Dannals, Robert F.

AU - Horti, Andrew G.

N1 - Funding Information: The authors would like to thank Dr. William H. Bunnelle (Abbott Laboratories) for helpful discussions and Mrs. Judy Buchanan for editorial assistance. This research was supported in part by the Division of Nuclear Medicine of Johns Hopkins University School of Medicine and by NIH Grants DA020777 and MH079017 (A.H.).

PY - 2012/6/15

Y1 - 2012/6/15

N2 - The radiosynthesis and in vivo evaluation of 5-(5-(6-[11C] methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [ 11C]rac-(1), a potential PET tracer for α7 nicotinic acetylcholine receptors (α7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation of 7 with [ 11C]CH3I afforded [11C]rac-1 in an average radiochemical yield of 30 ± 5% (n = 5) with high radiochemical purity and an average specific radioactivity of 444 ± 74 GBq/μmol (n = 5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [11C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal α7-nAChRs.

AB - The radiosynthesis and in vivo evaluation of 5-(5-(6-[11C] methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [ 11C]rac-(1), a potential PET tracer for α7 nicotinic acetylcholine receptors (α7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation of 7 with [ 11C]CH3I afforded [11C]rac-1 in an average radiochemical yield of 30 ± 5% (n = 5) with high radiochemical purity and an average specific radioactivity of 444 ± 74 GBq/μmol (n = 5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [11C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal α7-nAChRs.

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