Developing new PET tracers to image the growth hormone secretagogue receptor 1a (GHS-R1a)

Introduction: `The growth hormone secretagogue receptor 1a (GHS-R1a) is the orphan G-protein-coupled receptor,
and its endogenous ligand is ghrelin. GHS-R1a contributes to regulation of glucose homeostasis,memory and learning,
food addiction, and neuroprotection. Several PET tracers for GHS-R1a have been developed, but none have been reported
to be clinically applicable to GHS-R1a imaging. In this study, we developed three new PET tracers for GHSR1a:
18F-labeled 6-(4-chlorophenyl)-3-((1-(2-fluoroethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-one
(1), 11C-labeled 6-(4-chlorophenyl)-3-((1-(2-methoxyethyl)piperidin-3-yl)methyl)-2-(o-tolyl)quinazolin-4(3H)-
one (2), and 11C-labeled (S)-(4-(1H-indole-6-carbonyl)-3-methylpiperazin-1-yl)(4′-methoxy-[1,1′-biphenyl]-4-
yl)methanone (3).
Methods: [18F]1was synthesized by the 18F-fluoroethylation; [11C]2 or [11C]3 was synthesized by the 11C-methylation.
Biodistribution studies and PET studies were conducted in mice.
Results:Wesuccessfully radiosynthesized [18F]1, [11C]2, and[11C]3 with appropriate radioactivity for the animal study.
In the ex vivo biodistribution study, 60 min following injection, the radioactivity level of [18F]1 was relatively high in
the small intestine, that of [11C]2was high in the liver, and that of [11C]3was high in the pancreas. The radioactivity
levels of the three PET tracerswere relatively low in the brain. Under pretreatmentwith YIL781 (a selective and high
affinity antagonist for GHS-R1a), the pancreas radioactivity level at 30min following [11C]3 injectionwas significantly
reduced to 55% of control, but the radioactivity in the brain was not changed. In the PET study under control conditions,
high radioactivity levels in the liver and pancreas were observed following [11C]3 injection. With YIL781 pretreatment,
the accumulated radioactivity in the pancreas 15–60 min after [11C]3 injection was significantly
decreased to 78% of control.
Conclusion: [11C]3 exhibited relatively high uptake and in vivo specific binding to GHS-R1a in the mouse pancreas.
[11C]3 may be a useful PET tracers for in vivo imaging of GHS-R1a in the pancreas.

書誌情報

Nuclear Medicine and Biology

巻 52, p. 49-56, 発行日 2017-06

出版者

Elsevier

ISSN

収録物識別子タイプ

ISSN

収録物識別子

0969-8051

DOI

識別子タイプ

DOI

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2023-05-15 23:28:40.486676

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