Simplified quantification of nicotinic receptors with 2[ 18F]F -A-85380 PET

Abstract

Introduction Neuronal nicotinic acetylcholine receptors (nAChRs), widely distributed in the human brain, are implicated in various neurophysiological processes as well as being particularly affected in neurodegenerative conditions such as Alzheimer's disease. We sought to evaluate a minimally invasive method for quantification of nAChR distribution in the normal human brain, suitable for routine clinical application, using 2[ 18F]F -A-85380 and positron emission tomography (PET). Methods Ten normal volunteers (four females and six males, aged 63.40±9.22 years) underwent a dynamic 120-min PET scan after injection of 226 MBq 2[ 18F]F -A-85380 along with arterial blood sampling. Regional binding was assessed through standardized uptake value (SUV) and distribution volumes (DV) obtained using both compartmental (DV 2CM) and graphical analysis (DV Logan). A simplified approach to the estimation of DV (DV simplified), defined as the region-to-plasma ratio at apparent steady state (90–120 min post injection), was compared with the other quantification approaches. Results DV Logan values were higher than DV 2CM. A strong correlation was observed between DV simplified, DV Logan ( r=.94) and DV 2CM ( r=.90) in cortical regions, with lower correlations in thalamus ( r=.71 and .82, respectively). Standardized uptake value showed low correlation against DV Logan and DV 2CM. Conclusion DV simplified determined by the ratio of tissue to metabolite-corrected plasma using a single 90- to 120-min PET acquisition appears acceptable for quantification of cortical nAChR binding with 2[ 18F]F -A-85380 and suitable for clinical application.