Synthesis and characterization of a novel 18F-labeled 2, 5-diarylnicotinamide derivative targeting orexin 2 receptor. Issue 12 (18th November 2019)

• Record Type: Journal Article
• Authors: Watanabe, Hiroyuki; Matsushita, Naoki; Shimizu, Yoichi; Iikuni, Shimpei; Nakamoto, Yuji; Togashi, Kaori; Ono, Masahiro
• Is Part Of: MedChemComm. Volume 10:Issue 12(2019)
• Page Start: 2126
• Page End: 2130
• Publication Date: 2019-11-18
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c9md00397e
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : A novel 18 F labeled probe ([ 18 F]DAN-1) selectively bound to orexin 2 receptor (OX2 R) and displayed moderate uptake into the mouse brain. Abstract : Orexin 2 receptor (OX2 R) is thought to play an important role in the arousal-promoting function, but its distribution and function in the pathophysiology of orexin-mediated disorders remains to be fully elucidated. In the present study, we synthesized and characterized a novel 18 F-labeled 2, 5-diarylnicotinamide (DAN) derivative as a potential positron emission tomography (PET) probe for in vivo imaging of OX2 R. In in vitro binding experiments, [ 18 F]DAN-1 selectively bound to OX2 R. In a biodistribution study using normal mice, [ 18 F]DAN-1 displayed moderate brain uptake (2.10% ID per g at 10 min post-injection). In addition, the radioactivity in the mouse brain at 30 min post-injection was significantly decreased by co-injection with nonradioactive DAN-1, but high nonspecific binding was observed. These results suggested that further structural modifications of [ 18 F]DAN-1 are needed to use it for imaging OX2 R in the brain.