Ex Vivo Characterization of a Novel Iodine-123-Labelled Aminomethylchroman as a Potential Agonist Ligand for SPECT Imaging of Dopamine D2/3Receptors

For imaging of dopamine D 2/3 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 D 2/3 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 D 2/3 receptors in vitro, and here we report on the characterization of this first [ 123 I]-labelled D 2/3 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 D 2/3 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 D 2/3 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 .