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

✍ Scribed by Christian Loc'h; Lars Müller; Michèle Ottaviani; Christer Halldin; Lars Farde; Bernard Mazière

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: French
• Weight: 337 KB
• Volume: 36
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.2580360412

✦ Synopsis

2~-carbomethoxy-3~-(4-["Br]bromophenyI)tropane (f6Br]P-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 (PCIT) and a Cu' assisted bromodeiodination exchange. After purification by solid phase extraction and reverse phase HPLC, the chemical and radiochemical purities of f6Br]P-CBT were >98% and the specific radioactivity was 20 GBqlpmol. 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 [76Br]pCBT mainly labelled the dopamine transporter and bound to a single population of sites in striatal membranes ( B , , , = 6.5 pmollmg 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.