Parent M, Rosa-Neto P, Aliaga A, Soucy J-P, Bedard M-A (2011) [18F] fluoroethoxybenzovesamicol (FEOBV): A reliable PET radiocompound for the in-vivo assessment of cholinergic terminals. Neuroscience 2011 Abstracts 37.13. Society for Neuroscience, Washington, DC.
Summary: The vesicular acetylcholine transporter (VAChT) can be used as a surrogate target for PET imaging of brain cholinergic terminals. [18F]fluoroethoxybenzovesamicol (FEOBV) appears as a promising VAChT radioligand for PET imaging (Mulholand et al., 1998). Its pharmacokinetics, metabolism, and brain distribution have been well described in rodent and in primates (Kilbourn et al., 2010; Landry-St-Pierre et al., 2006; Soucy et al., 2010). The current study aims to assess the availability of VAChT binding sites in animals with presynaptic deficits induced by age or experimental lesions. We predict declines of FEOBV binding in brain regions innervated by cholinergic fibers. Twenty-one male Long-Evans rats were evenly divided in three groups: 1) Young rats (one month old); 2) Older rats (18 months old); 3) Rats with unilateral cholinergic lesions. In the latter group, 192-IgG-saporin (0.5 μg/μl) was infused under stereotaxic control into the nucleus basalis magnocellularis (NBM). A three weeks recovery period followed the surgery. FEOBV PET was conducted with a microPET (Siemens R4) on anesthetized animals. FEOBV (~11MBq) was injected and radioactivity measured in 27 sequential time frames of increasing duration, from 30 s to 5 min, for a total duration of 60 min. Images were reconstructed using a Maximum A Posteriori (MAP) algorithm, coregistered to a typical rat MRI template, and binding potential (BP) was calculated using the cerebellar cortex as reference tissue. Student t-tests were carried out at the voxel level: 1) Between lesioned (n=7) and non-lesioned (n=14) rats; 2) Between young (n=7) and old (n=7) non-lesioned rats. In lesioned rats, maximal BP reduction was observed in the ventral frontal cortex on the side of the lesion (t=6.5, p<0.0005, µ=41.88 mm3). Aged rats show significant clusters of BP reduction in both hippocampi (t=7.5 p<0.0005 24.61 mm3). We conclude that FEOBV PET allows quantification of cholinergic denervation following both normal aging and surgically induced cholinergic lesions.
Related Products: 192-IgG-SAP (Cat. #IT-01)