Quantification of brain cholinergic denervation in Alzheimer's disease using PET imaging with [18F]-FEOBV.

ABSTRACT

18F-fluoroethoxybenzovesamicol (FEOBV) is a new PET radiotracer that binds to the vesicular acetylcholine transporter. In both animals and healthy humans, FEOBV was found sensitive and reliable to characterize presynaptic cholinergic nerve terminals in the brain. It has been used here for we believe the first time in patients with Alzheimer's disease (AD) to quantify brain cholinergic losses. The sample included 12 participants evenly divided in healthy subjects and patients with AD, all assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) cognitive scales. Every participant underwent three consecutive PET imaging sessions with (1) the FEOBV as a tracer of the cholinergic terminals, (2) the 18F-NAV4694 (NAV) as an amyloid-beta tracer, and (3) the 18F-Fluorodeoxyglucose (FDG) as a brain metabolism agent. Standardized uptake value ratios (SUVRs) were computed for each tracer, and compared between the two groups using voxel wise t-tests. Correlations were also computed between each tracer and the cognitive scales, as well as between FEOBV and the two other radiotracers. Results showed major reductions of FEOBV uptake in multiple cortical areas that were evident in each AD subject, and in the AD group as a whole when compared to the control group. FDG and NAV were also able to distinguish the two groups, but with lower sensitivity than FEOBV. FEOBV uptake values were positively correlated with FDG in numerous cortical areas, and negatively correlated with NAV in some restricted areas. The MMSE and MoCA cognitive scales were found to correlate significantly with FEOBV and with FDG, but not with NAV. We concluded that PET imaging with FEOBV is more sensitive than either FDG or NAV to distinguish AD patients from control subjects, and may be useful to quantify disease severity. FEOBV can be used to assess cholinergic degeneration in human, and may represent an excellent biomarker for AD.