SYNTHESIS OF -CARBOMETHOXY-3-BETA-(4-[BR-76]BROMOPHENYL)TROPANE ([BR-76]BETA-CBT), A PET TRACER FOR IN-VIVO IMAGING OF THE DOPAMINE UPTAKE SITES

2 beta-carbomethoxy-3 beta-(4-[Br-76]bromophenyl)tropane ([Br-76]beta- CBT) was prepared either by electrophilic substitution from the tribut yl-stannyl derivative and peracetic acid as oxidant or by nucleophilic substitution from the iodo analogue (beta-CIT) and a Cu+ assisted bro modeiodination exchange. After purification by solid phase extraction and reverse phase HPLC, the chemical and radiochemical purities of [Br -76]beta-CBT were >98% and the specific radioactivity was 20 GBq/mu mo l. Using the two labelling techniques, the radiochemical yields were 8 0% and 60%, respectively. From the deshalogeno compound and different oxidizing conditions, the radiolabelling yields were <5%. In vitro com petition and saturation pharmacological studies showed that [Br-76]bet a-CBT mainly labelled the dopamine transporter and bound to a single p opulation of sites in striatal membranes (B-max = 6.5 pmol/mg protein) with an apparent dissociation constant of 2.8 nM. Biodistribution and autoradiography studies of the title compound in rats showed that 3 h post injection, the highest concentration in the brain was found in t he striata (2.5% ID/g). 24 h post injection, the striatum to cerebellu m radioactive concentration ratio was still 17.