Synthesis of 2β‐carbomethoxy‐3β‐(4‐[⁷⁶Br]bromophenyl)tropane ([⁷⁶Br]β‐CBT), a pet tracer for in vivo imaging of the dopamine uptake sites

Abstract 2β‐carbomethoxy‐3β‐(4‐[ 76 Br]bromophenyl)tropane ([ 76 Br]β‐CBT) was prepared either by electrophilic substitution from the tributyl‐stannyl derivative and peracetic acid as oxidant or by nucleophilic substitution from the iodo analogue (β‐CIT) and a Cu + assisted bromodeiodination exchange. After purification by solid phase extraction and reverse phase HPLC, the chemical and radiochemical purities of [ 76 Br]β‐CBT were > 98% and the specific radioactivity was 20 GBq/μmol. Using the two labelling techniques, the radiochemical yields were 80% and 60%, respectively. From the deshalogeno compound and different oxidizing conditions, the radiolabelling yields were < 5%. In vitro competition and saturation pharmacological studies showed that [ 76 Br]β‐CBT mainly labelled the dopamine transporter and bound to a single population 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 the striata (2.5% ID/g). 24 h post injection, the striatum to cerebellum radioactive concentration ratio was still 17.