In vivo evaluation of [C-11]- and [F-18]-labelled cocaine analogues as potential dopamine transporter ligands for positron emission tomography

Four analogues of the potent dopamine transporter ligand, WIN 35,428, were radiolabelled with C-11 and F-18 at the 2-beta-carboxy position for evaluation as potential ligands for imaging dopamine uptake sites by positron emission tomography (PET) namely, methyl (1R-2-exo-3-exo)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxy (RTI-32), its 4-chlorophenyl analogue (RTI-31), 2'-fluoro- ethyl (1R-2-exo-3-exo)-8 methyl-3-(4-methylphe (FETT) and its 4-chlorophenyl analogue (FECT). Upon intravenous injection in rats, all four radiotracers displayed preferential accumulation of radioactivity in regions known to contain high concentrations of dopamine uptake sites. Competition studies with two of the analogues, [C-11]RTI-32 and [F-18]FETT, demonstrated that, for both radiotracers, binding was saturable and displayed the appropriate pharmacology as potential PET ligands for imaging the dopamine transporter. Striatum to cerebellar ratios for [C-11]RTI-32 (at 90 min post-injection) and [F-18]FETT (at 120 min post injection) were 27 and 21, respectively.