PET Imaging of brain muscarinic receptors with 18F-Fluorobenzyl-Dexetimide: A first in human study.

Abstract

M1 and M4 muscarinic receptor (mAChR) agonists are under development for the treatment of schizophrenia, Alzheimer's and Parkinson's disease. We performed first-in-human PET imaging of mAChR with 18F-Fluorobenzyl-Dexetimide (FDEX) in 10 healthy participants (29.4±4.3yrs). Four underwent dynamic brain scanning for 240 min, and then six underwent static brain scans at 120 and 160-min post injection of 250 MBq of FDEX. Gjedde-Patlak graphical analysis was applied to determine the influx constant (Ki). Regional tissue ratios (SUVR) were calculated using the cerebellar cortex as the reference region. No adverse events were observed. The tracer showed good brain entry (∼4.2% ID at 5 min) but irrev..