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Current Radiopharmaceuticals

Editor-in-Chief

ISSN (Print): 1874-4710
ISSN (Online): 1874-4729

Research Article

Development of a Novel Carbon-11 Labeled PET Radioligand for Melanin- Concentrating Hormone Receptor 1

Author(s): Hideyuki Igawa, Vladimir Stepanov, Lenke Tari, Shoki Okuda, Syunsuke Yamamoto, Shizuo Kasai, Yasutaka Nagisa, Jenny Haggkvist, Marie Svedberg, Miklos Toth, Akihiro Takano and Christer Halldin

Volume 10, Issue 1, 2017

Page: [35 - 40] Pages: 6

DOI: 10.2174/1874471009666161230113630

Price: $65

Abstract

Background and Objective: Melanin-concentrating hormone (MCH) is an attractive target for antiobesity agents and many drug discovery programs have been dedicated to identify smallmolecule antagonists of melanin-concentrating hormone receptor 1 (MCHR1). The aim of this study was to develop a positron emission tomography (PET) tracer for MCHR1 for translation of preclinical pharmacology to clinic to enhance success rate of drug discovery programs.

Methods: We identified 4-(cyclopropylmethoxy)-N-[8-methyl-3-({[(1-methyl-1H-pyrrol-2-yl)methyl] amino}ethyl)quinolin-7-yl]benzamide (Compound II) from Takeda MCHR1 antagonist library by utilizing binding affinity, log D value, physicochemical parameters ideal for a central nerve system agent, and synthetic feasibility of corresponding carbon-11 labeled radioligands as selection parameters for tracer candidates.

Results: In the rat PET study, [11C] Compound II showed clear uptake in the caudate/putamen with the pretreatment of cyclosporine A and its uptake was higher than that in the cerebellum where expression of MCHR1 was reported to be low.

Conclusion: In summary, [11C]Compound II is a promising lead compound for developing a suitable MCHR1 PET radioligand. [11C]Compound II, in combination with cyclosporine A, could be used as a research tool to visualize and quantify MCHR1 in rodents.

Keywords: Carbon-11, positron emission tomography (PET), PET radioligand, MCHR1, cyclosporine A, brain imaging.

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