Graphical analysis of 2-[18F]FA binding to nicotinic acetylcholine receptors in rhesus monkey brain

External imaging of nicotinic acetylcholine receptors (nAChRs) using techniques such as PET would help to clarify the roles of these receptors in the physiology and pathology of brain function. Here we report the results of quantitative PET studies of cerebral nAChRs with 2‐[18F]fluoro‐A‐85380 (2‐[18F]FA) in rhesus monkeys. Data from dynamic PET scans were analyzed using graphical methods. Binding potential (BP) values of 2.0, 0.4, 0.3, and 0.03 observed in the thalamus (Th), cortex (Cx), striatum (Str), and cerebellum (Cb), respectively, were consistent with the pattern of α4β2 nAChR distribution in monkey brain. The high value of 2‐[18F]FA‐specific binding in the rhesus monkey Th and low level of that in Cb compared with nonspecific accumulation of radioactivity in these structures allowed use of Cb as a reference region for calculation of BP and volume of distribution of specific binding (VDsb) in Th by graphical methods, both with and without the plasma input function. In contrast, estimation of 2‐[18F]FA specific binding in low‐receptor‐density regions such as Cx and Str required assessment of nondisplaceable volume of distribution (VDnd) in a separate study and measurement of nonmetabolized radioligand concentrations in the plasma. For accurate quantitation of 2‐[18F]FA‐specific binding by graphical analysis, PET studies should last up to 7 h due to the slow kinetics of 2‐[18F]FA brain distribution. Further, to avoid substantial underestimation in measured BP values the doses of administered 2‐[18F]FA should not exceed 0.1 nmol/kg body weight. The findings suggest that 2‐[18F]FA is a promising ligand for quantitation of nAChRs in human brain. Synapse 48:25–34, 2003. Published 2003 Wiley‐Liss, Inc.