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Current Radiopharmaceuticals


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


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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