[F-18]CFT ([F-18]WIN-35,428), A RADIOLIGAND TO STUDY THE DOPAMINE TRANSPORTER WITH PET - BIODISTRIBUTION IN RATS

We describe the F-18-radiolabelling synthesis (F-18; T-1/2=109.8 min) of 2-beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (also known as C FT or WIN 35,428) and the biodistribution of this compound in rats. F- 18-labelled CFT has high chemical and radiochemical purity and relativ ely high specific radioactivity [specific radioactivity up to 14.8 GBq /mu mol (400 mCi/mu mol) at end of synthesis]. Striatum to cerebellum radioactivity uptake ratios were calculated from digitised images of r at brain slices recorded with a phosphoimaging device, the maximum rat io of about 10 was obtained at 2 h postinjection. Pretreatment of the rats with a specific dopamine transport inhibitor, GBR 12909, showed t hat CFT binding is specific in striatum. The highest accumulation of F -18-radioactivity was found in the liver, urine, striatum, and kidney of the rat. Clearance from blood was rapid. The uptake in bone was low , indicating that [F-18]CFT is not defluorinated. The relatively long half-life of F-18 makes it possible to study the uptake of [F-18]CFT i n the brain, as equilibrium between specific and non-specific binding is reached. This will improve the signal to noise ratio as compared to positron emission tomography (PET) studies with [C-11]CFT (C-11; T-1/ 2=20.4 min). CFT labelled with F-18 is clearly a promising radioligand for PET studies of the dopamine transporter system in humans. (C) 199 6 Wiley-Liss, Inc.