PET imaging of cholinergic deficits in rats using [18F]fluoroethoxybenzovesamicol ([18F]FEOBV)

Abstract

[(18)F]fluoroethoxybenzovesamicol ([(18)F]FEOBV) is one of the most promising radioligands for imaging the vesicular ACh transporter (VAChT) with positron emission tomography (PET). We report here that this method can detect subtle cholinergic terminals losses such as those associated with aging, or those following a partial lesion of the nucleus basalis magnocellularis (NBM). Twenty-one adult rats were evenly distributed in three groups including 1) aged rats (18 months); 2) young rats (3 months); and 3) rats with unilateral lesion of the NBM, following a local stereotaxic infusion of 192 IgG-saporin. In both normal and lesioned rats, our results revealed the highest [(18)F]FEOBV binding to be in the striatum, followed by similar values in both frontal cortex and thalamus, while lower values were observed in both hippocampus and temporo-parietal cortex. This binding distribution is consistent with the known anatomy of brain cholinergic systems. In the lesioned rats, [(18)F]FEOBV binding was found to be reduced mostly in the ventral frontal cortex on the side of the lesion, but some reductions were also observed in the homologous region of the contralateral hemisphere. Aging was found to be associated with a [(18)F]FEOBV binding reduction limited to the hippocampus of both hemispheres. [(18)F]FEOBV appears to be a very promising marker for the in vivo quantification of the brain VAChT; PET imaging of this agent allows in vivo detection of both physiological and pathological reductions of cholinergic terminals density.