title: Ex Vivo Characterization of a Novel Iodine-123-Labelled Aminomethylchroman as a Potential Agonist Ligand for SPECT Imaging of Dopamine D2/3 Receptors.
abstract: For imaging of dopamine D2/3 receptors, agonist tracers are favoured over antagonists because they are more sensitive to detection of dopamine release and because they may selectively label the high-affinity receptor state. We have developed novel D2/3 receptor selective agonists that can be radiolabelled with [(123)I], which label is advantageous over most other labels, such as carbon-11, as it has a longer half-life. Particularly, we considered (R) N-[7-hydroxychroman-2-yl]-methyl 4-iodobenzyl amine (compound 1) as an attractive candidate for development as it shows high binding affinity to D2/3 receptors in vitro, and here we report on the characterization of this first [(123)I]-labelled D2/3 receptor agonist radiopharmaceutical intended for SPECT imaging. The appropriate tin precursor for [(123)I]-1 was developed and was successfully radiolabelled with iodine-123 giving a moderate yield (30-35%) and a good purity (>95%) for [(123)I]-1. In biodistribution experiments in Wistar rats intravenous injection of [(123)I]-1 resulted in a fast brain uptake, where the observed binding in the D2/3 receptor-rich striatum was slightly higher than that in the cerebellum 30 min to 4 h p.i. Storage phosphor imaging experiments, however, did not show specific D2/3 receptor binding. In conclusion, despite promising in vitro data for 1, neither specific ex vivo binding nor high signal-to-noise ratios were found in rodents for [(123)I]-1.
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: van Wieringen
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.
authors.forename: Kora
authors.initials: K
authors.lastname: de Bruin
authors.affiliation: SyMO-Chem BV, Den Dolech 2, 5612 AZ Eindhoven, Netherlands.
authors.forename: Henk M
authors.initials: HM
authors.lastname: Janssen
authors.affiliation: SyMO-Chem BV, Den Dolech 2, 5612 AZ Eindhoven, Netherlands.
authors.forename: P Michel
authors.initials: PM
authors.lastname: Fransen
authors.affiliation: GE Healthcare, De Rondom 8, 5612 AP Eindhoven, Netherlands.
authors.forename: Anton G M
authors.initials: AG
authors.lastname: Janssen
authors.affiliation: GE Healthcare, De Rondom 8, 5612 AP Eindhoven, Netherlands.
authors.forename: Peter A
authors.initials: PA
authors.lastname: van Doremalen
authors.affiliation: Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Straße 67, 55101 Mainz, Germany.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Booij