Dopamine transporter binding in rat striatum: a comparison of [O-methyl-11C]β-CFT and [N-methyl-11C]β-CFT

Introduction: Positron emission tomography scanning with radiolabeled phenyltropane cocaine analogs is important for quantifying the in vivo density of monoamine transporters, including the dopamine transporter (DAT). [11C]β-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [11C]β-CFT is commonly labeled at the N-methyl position. However, labeling of [11C]β-CFT at the O-methyl position is a simpler procedure and results in a shorter synthesis time [desirable in small-animal studies, where specific activity (SA) is crucial]. In this study, we sought to validate that the O-methylated form of [11C]β-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form. Methods: Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-11C]β-CFT and once with [O-methyl-11C]β-CFT. DAT binding potentials (BP≡B'avail/Kd) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function. Results: [N-Methyl-11C]β-CFT and [O-methyl-11C]β-CFT were synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical purity was >99%. SA at end of bombardment was 258±30 GBq/μmol. Average BP values for right and left striata with [N-methyl-11C]β-CFT were 1.16±0.08 and 1.23±0.14, respectively. BP values for [O-methyl-11C]β-CFT were 1.18±0.08 (right) and 1.22±0.16 (left). Paired t tests demonstrated that labeling position did not affect striatal DAT BP. Conclusions: These results suggest that [O-methyl-11C]β-CFT is quantitatively equivalent to [N-methyl-11C]β-CFT in the rat striatum