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

Abstract 

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/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-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.

Keywords: Positron emission tomography, Dopamine transporter, [¹¹C]β-CFT, Striatum, Dopamine, Animal models