Concordance between in vivo and postmortem measurements of cholinergic denervation in rats using PET with [(18)F]FEOBV and choline acetyltransferase immunochemistry

BACKGROUND: Fluorine-18 fluoroethoxybenzovesamicol ([(18)F]FEOBV) is a radioligand for the selective imaging of the vesicular acetylcholine transporter with positron emission tomography (PET). The current study demonstrates that pathological cortical cholinergic deafferentation can be quantified in vivo with [(18)F]FEOBV PET, yielding analogous results to postmortem histological techniques. METHODS: Fifteen male rats (3 months old) underwent a cerebral infusion of 192 IgG-saporin at the level of the nucleus basalis magnocellularis. They were scanned using [(18)F]FEOBV PET, then sacrificed, and their brain tissues collected for immunostaining and quantification of cholinergic denervation using optical density (OD). RESULTS: For both PET binding and postmortem OD, the highest losses were found in the cortical areas, with the highest reductions in the orbitofrontal, sensorimotor, and cingulate cortices. In addition, OD quantification in the affected areas accurately predicts [(18)F]FEOBV uptake in the same regions when regressed linearly. CONCLUSIONS: These findings support [(18)F]FEOBV as a reliable imaging agent for eventual use in human neurodegenerative conditions in which cholinergic losses are an important aspect.