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). [(11)C]beta-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [(11)C]beta-CFT is commonly labeled at the N-methyl position. However, labeling of [(11)C]beta-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 [(11)C]beta-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-(11)C]beta-CFT and once with [O-methyl-(11)C]beta-CFT. DAT binding potentials (BP identical withB'(avail)/K(d)) 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-(11)C]beta-CFT and [O-methyl-(11)C]beta-CFT were synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical purity was >99%. SA at end of bombardment was 258+/-30 GBq/micromol. Average BP values for right and left striata with [N-methyl-(11)C]beta-CFT were 1.16+/-0.08 and 1.23+/-0.14, respectively. BP values for [O-methyl-(11)C]beta-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-(11)C]beta-CFT is quantitatively equivalent to [N-methyl-(11)C]beta-CFT in the rat striatum.