Synthesis and biodistribution of [11C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2)

Andrew G. Horti; Yongjun Gao; Hayden T. Ravert; Paige Finley; Heather Valentine; Dean F. Wong; Christopher J. Endres; Alena V. Savonenko; Robert F. Dannals

doi:10.1016/j.bmc.2010.05.058

Synthesis and biodistribution of [¹¹C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB₂)

Andrew G. Horti, Yongjun Gao, Hayden T. Ravert, Paige Finley, Heather Valentine, Dean F. Wong, Christopher J. Endres, Alena V. Savonenko, Robert F. Dannals

School of Medicine

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

71 Scopus citations

Abstract

Recently, A-836339 [2,2,3,3-tetramethylcyclopropanecarboxylic acid [3-(2-methoxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]amide] (1) was reported to be a selective CB₂ agonist with high binding affinity. Here we describe the radiosynthesis of [¹¹C]A-836339 ([¹¹C]1) via its desmethyl precursor as a candidate radioligand for imaging CB₂ receptors with positron-emission tomography (PET). Whole body and the regional brain distribution of [¹¹C]1 in control CD1 mice demonstrated that this radioligand exhibits specific uptake in the CB₂-rich spleen and little specific in vivo binding in the control mouse brain. However, [ ¹¹C]1 shows specific cerebral uptake in the lipopolysaccharide (LPS)-induced mouse model of neuroinflammation and in the brain areas with Aβ amyloid plaque deposition in a mouse model of Alzheimer's disease (APPswe/PS1dE9 mice). These data establish a proof of principle that CB ₂ receptors binding in the neuroinflammation and related disorders can be measured in vivo.

Original language	English (US)
Pages (from-to)	5202-5207
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	14
DOIs	https://doi.org/10.1016/j.bmc.2010.05.058
State	Published - Jul 15 2010

Keywords

Alzheimer's disease
CB receptor
Cannabinoid receptor
Neuroinflammation
PET
Positron-emission tomography

ASJC Scopus subject areas

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

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10.1016/j.bmc.2010.05.058

Cite this

@article{e20e65f29bc3447591e129ce8fe7b04f,

title = "Synthesis and biodistribution of [11C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2)",

abstract = "Recently, A-836339 [2,2,3,3-tetramethylcyclopropanecarboxylic acid [3-(2-methoxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]amide] (1) was reported to be a selective CB2 agonist with high binding affinity. Here we describe the radiosynthesis of [11C]A-836339 ([11C]1) via its desmethyl precursor as a candidate radioligand for imaging CB2 receptors with positron-emission tomography (PET). Whole body and the regional brain distribution of [11C]1 in control CD1 mice demonstrated that this radioligand exhibits specific uptake in the CB2-rich spleen and little specific in vivo binding in the control mouse brain. However, [ 11C]1 shows specific cerebral uptake in the lipopolysaccharide (LPS)-induced mouse model of neuroinflammation and in the brain areas with Aβ amyloid plaque deposition in a mouse model of Alzheimer's disease (APPswe/PS1dE9 mice). These data establish a proof of principle that CB 2 receptors binding in the neuroinflammation and related disorders can be measured in vivo.",

keywords = "Alzheimer's disease, CB receptor, Cannabinoid receptor, Neuroinflammation, PET, Positron-emission tomography",

author = "Horti, {Andrew G.} and Yongjun Gao and Ravert, {Hayden T.} and Paige Finley and Heather Valentine and Wong, {Dean F.} and Endres, {Christopher J.} and Savonenko, {Alena V.} and Dannals, {Robert F.}",

note = "Funding Information: The authors thank Drs. Mikhail Pletnikov and Catherine A. Foss for fruitful discussions, Dr. Richard L. Wahl for fruitful discussions and support and Dr. Ursula Scheffel for help with animal experiments. The authors thank Ms. Judy Buchanan for editorial assistance. This research was supported in part by the NIH Grant MH079017 (A.G.H.) and the Division of Nuclear Medicine, Johns Hopkins School of Medicine . ",

year = "2010",

month = jul,

day = "15",

doi = "10.1016/j.bmc.2010.05.058",

language = "English (US)",

volume = "18",

pages = "5202--5207",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

number = "14",

}

TY - JOUR

T1 - Synthesis and biodistribution of [11C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2)

AU - Horti, Andrew G.

AU - Gao, Yongjun

AU - Ravert, Hayden T.

AU - Finley, Paige

AU - Valentine, Heather

AU - Wong, Dean F.

AU - Endres, Christopher J.

AU - Savonenko, Alena V.

AU - Dannals, Robert F.

N1 - Funding Information: The authors thank Drs. Mikhail Pletnikov and Catherine A. Foss for fruitful discussions, Dr. Richard L. Wahl for fruitful discussions and support and Dr. Ursula Scheffel for help with animal experiments. The authors thank Ms. Judy Buchanan for editorial assistance. This research was supported in part by the NIH Grant MH079017 (A.G.H.) and the Division of Nuclear Medicine, Johns Hopkins School of Medicine .

PY - 2010/7/15

Y1 - 2010/7/15

N2 - Recently, A-836339 [2,2,3,3-tetramethylcyclopropanecarboxylic acid [3-(2-methoxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]amide] (1) was reported to be a selective CB2 agonist with high binding affinity. Here we describe the radiosynthesis of [11C]A-836339 ([11C]1) via its desmethyl precursor as a candidate radioligand for imaging CB2 receptors with positron-emission tomography (PET). Whole body and the regional brain distribution of [11C]1 in control CD1 mice demonstrated that this radioligand exhibits specific uptake in the CB2-rich spleen and little specific in vivo binding in the control mouse brain. However, [ 11C]1 shows specific cerebral uptake in the lipopolysaccharide (LPS)-induced mouse model of neuroinflammation and in the brain areas with Aβ amyloid plaque deposition in a mouse model of Alzheimer's disease (APPswe/PS1dE9 mice). These data establish a proof of principle that CB 2 receptors binding in the neuroinflammation and related disorders can be measured in vivo.

AB - Recently, A-836339 [2,2,3,3-tetramethylcyclopropanecarboxylic acid [3-(2-methoxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]amide] (1) was reported to be a selective CB2 agonist with high binding affinity. Here we describe the radiosynthesis of [11C]A-836339 ([11C]1) via its desmethyl precursor as a candidate radioligand for imaging CB2 receptors with positron-emission tomography (PET). Whole body and the regional brain distribution of [11C]1 in control CD1 mice demonstrated that this radioligand exhibits specific uptake in the CB2-rich spleen and little specific in vivo binding in the control mouse brain. However, [ 11C]1 shows specific cerebral uptake in the lipopolysaccharide (LPS)-induced mouse model of neuroinflammation and in the brain areas with Aβ amyloid plaque deposition in a mouse model of Alzheimer's disease (APPswe/PS1dE9 mice). These data establish a proof of principle that CB 2 receptors binding in the neuroinflammation and related disorders can be measured in vivo.

KW - Alzheimer's disease

KW - CB receptor

KW - Cannabinoid receptor

KW - Neuroinflammation

KW - PET

KW - Positron-emission tomography

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SN - 0968-0896

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JO - Bioorganic and Medicinal Chemistry

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