In vivo imaging of brain muscarinic receptors with ¹⁸F-Flurobenzyl Dexetimide: First in human studies

Background: Muscarinic receptors are involved in neurodegenerative disease such as Alzheimer’s and Parkinson’s diseases, as well as in psychiatric conditions such as schizophrenia and depression. We performed a first in human study with ¹⁸F-Flurobenzyl-Dexetimide (FDEX) to measure levels of muscarinic receptors (mAChR) in the brain of healthy control subjects.

Methods: Ten healthy participants (29.4±4.3 yo, 50%F) were enrolled in the study. Four participants underwent dynamic brain scanning for 240 min, while the other 6 underwent brain scans at 120 and 160-min post injection (mpi) of 200 MBq of FDEX and serial whole-body PET scans to determine tracer dosimetry. Gjedde-Patlak graphical analysis was applied to determine the influx constant (Ki), and tissue ratios (SUVR) at 120 and 160 mpi were calculated for all participants in the frontal, hippocampus and putamen regions, using the cerebellar cortex as reference region.

Results: No adverse events related to the study drug were observed or reported by the subjects following the FDEX scan. Tracer showed good entry into the brain (~4.2% ID at 5 min) and displayed irreversible kinetics during the scanning period (Fig 1). Tracer uptake was higher in the putamen -K_i 0.42±0.04; SUVR120 3.23±0.24 and SUVR160 3.75±0.27-, followed by frontal -K_i 0.27±0.01; SUVR120 2.61±0.26 and SUVR160 2.95±0.27-, and hippocampus -K_i 0.25±0.02; SUVR120 2.03±0.17 and SUVR160 2.30±0.17-.

Conclusions: FDEX uptake in the brain showed little variance across subjects, suggesting FDEX might be a useful and robust tool to detect variations in muscarinic receptors in the brain.

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