IN-VITRO AND IN-VIVO CHARACTERIZATION OF R(-FIDA2 - A DOPAMINE D2-LIKE IMAGING AGENT())

R(+)-FIDA2, 4'-fluorobenzyl)-2-pyrrolidinyl)-methyl]benzamide, is a ne w dopamine D2-like receptor imaging agent that can be labeled with eit her I-123 or F-18 for SPECT or PET imaging. The purpose of this study was to characterize its in vitro and in vivo binding properties. Metho ds: In vitro binding studies using [I-125]R(+)-FIDA2 were performed in Sf9 cells expressing dopamine D2 or D3 receptors and in rat basal for ebrain homogenates, which contain a high density of dopamine D2-like r eceptors. A series of in vivo SPECT imaging studies in nonhuman primat es (cynomologous monkeys) were performed by intravenously injecting 7. 1 +/- 1.0 mCi of [I-123]R(+)-FIDA2. At least one control study and one displacement experiment, in which a cold compound was injected intrav enously 90 min after tracer injection, was performed in each monkey. D ata were acquired in 10-min frames for 180 min, and the activity in re gions of interest (basal ganglia and cerebellum) were plotted versus t ime. Results: iodine-125-R(+)-FIDA2 displayed K-d values for D2 and D3 receptor subtypes expressed in Sf9 cells of 0.11 and 0.04 nM, respect ively. As expected, SPECT images of monkey brain (transaxial sections, 2 mm) showed that the radioactivity was localized in the area of the basal ganglia and reached peak concentrations in 11.5 +/- 5.8 min post injection. An injection of R(+)7-OH-PIPAT, a new ligand that is select ive for dopamine D3 receptors and the high affinity state of dopamine D2 receptors, did not show significant displacement of [I-123]R(+)-FID A2 binding in the basal ganglia. Conclusion: These studies indicate th at R(+)-FIDA2 may be a useful ligand for in vitro pharmacological char acterization and in vivo imaging of CNS dopamine D2-like receptors.