PET Brain imaging of α7-nAChR with [¹⁸F]ASEM

Abstract

The α7 nicotinic acetylcholine receptor (nAChR) increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The α7-nAChR primarily is located in cerebral cortex and sub-cortical regions, compared to the α4β2 nAChR subtype that has a more subcortical distribution. The highly cortical distribution suggests a role of α7-nAChR in cognition. We expanded the first-in-human PET imaging of α7-nAChR with [ Median VT in a feasibility study of six patients with schizophrenia was lower than in healthy volunteers in cingulate cortex, frontal cortex, and hippocampus. Mann-Whitney test identified cingulate cortex and hippocampus as regions with significantly lower median VT in patients than in healthy volunteers when a single outlier patient was excluded from analysis (P = 0.02, corrected for multiple comparisons). peer-reviewed)

Investigation of the benefit of PVC in high resolution PET as a post and within reconstruction method for FDG brain data

“…Similar findings were observed in a recent study where the GTM method was applied on 5 people with AD and 6 healthy controls respectively using the amyloid tracers of [ 18 F ]florbetapir and [ 11 C]PiB. Results showed that PVC increases the discrimination between AD patients and the healthy controls [9].…”

PET Neuroimaging of Alzheimer's Disease: Radiotracers and Their Utility in Clinical Research

“…While most of the previous human PET studies used α 4 β 2 or non-selective nAChR tracers including [ 11 C]nicotine, 2-[ 18 F]F-A-85380 ([ 18 F]2-FA), [ 18 F]AZAN, and [ 18 F]flubatine (also known as [ 18 F]NCFHEB) (Figure 6) (Nordberg et al, 1990;Sabri et al, 2008Sabri et al, , 2015bWong et al, 2013), successful development of selective tracers for new targets such α 7 nAChR and M1 and M4 mAChR has been reported recently. Recent imaging evaluations in humans indicated that [ 18 F]ASEM, [ 11 C]LSN3172176, and [ 11 C]MK-6884 (Figure 6) have appropriate kinetics and imaging properties and are promising tracers for their respective targets α 7 nAChR and M1 and M4 mAChR (Hillmer et al, 2017;Wong et al, 2018;Masdeu et al, 2020;Tong et al, 2020;Naganawa et al, 2021b). [ 18 F]ASEM and [ 11 C]MK-6884 have been used in preliminary studies of α 7 nAChR and M4 mAChR in AD (see below), while evaluation of M1 mAChR in AD is ongoing with [ 11 C]LSN3172176 in our laboratories.…”