IN-VIVO EVALUATION OF [C-11] AND [F-18] LABELLED COCAINE ANALOGUES ASPOTENTIAL 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 f or evaluation as potential ligands for imaging dopamine uptake sites b y positron emission tomography (PET) namely, methyl -methylphenyl)-8-a zabicyclo[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 injecti on in rats, all four radiotracers displayed preferential accumulation of radioactivity in regions known to contain high concentrations of do pamine uptake sites. Competition studies with two of the analogues, [C -11]RTI-32 and [F-18]FETT, demonstrated that, for both radiotracers, b inding was saturable and displayed the appropriate pharmacology as pot ential PET ligands for imaging the dopamine transporter. Striatum to c erebellar 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.