title: Evaluation of novel tropane analogues in comparison with the binding characteristics of [18F]FP-CIT and [131I]beta-CIT.
abstract: This study evaluated novel potential dopamine transporter (DAT) inhibitors as ligands for positron emission tomography. Five new tropane analogs were synthesized and compared with the known ligand 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT) and the recently characterized ligands N-(3-iodoprop-2E-enyl)-2beta-carbomethoxy-3beta-(4-methylphenyl)-nortropane (PE2I) and 2beta-carbofluoroethoxy-3beta-(4-methylphenyl)tropane (FETT). Evaluation with autoradiography measured the ability to antagonize the binding of [(131)I]iodine-labeled beta-CIT and [(18)F]fluorine-labeled N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodo-phenyl) nortropane in rat and pig brains. The standards for comparison (PE2I and FETT) competed strongly in all regions investigated (striatum, cortex, superior colliculus and cerebellum). Of the new compounds, 2alpha-amido-fluoroethyl-3beta-(4-iodophenyl)tropane (4) and 2beta-amido-fluoroethyl-3beta-(4-iodophenyl)tropane (4a) competed strongly with [(131)I]beta-CIT in DAT-rich striatum, but also in other brain regions suggesting poor DAT selectivity. Because [(131)I]beta-CIT binds unselectively both to DAT and serotonin transporters, no definite conclusion about the selectivity of the new compounds is possible. However, preclinical studies using the compounds and labeled with fluorine-18 or iodine-131 are encouraged.
authors.affiliation: Institut für Nuklearchemie, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany. w.sihver@fz-juelich.de
authors.forename: W
authors.initials: W
authors.lastname: Sihver
authors.forename: B
authors.initials: B
authors.lastname: Drewes
authors.forename: A
authors.initials: A
authors.lastname: Schulze
authors.forename: R A
authors.initials: RA
authors.lastname: Olsson
authors.forename: H H
authors.initials: HH
authors.lastname: Coenen
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D011485:Protein Binding; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014326:Tropanes / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D014326:Tropanes; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine