Synthesis and initial evaluation of radioiodine-labelled deuterated tropane derivatives targeting dopamine transporter.

The dopamine transporter (DAT) is closely related to a variety of neurological disorders including Parkinson's disease (PD) and other neurodegenerative diseases. In vivo imaging of DAT with radio-labelled tracers has become a powerful technique in related disorders. The radioiodine-labelled tropane derivative [I]FP-CIT ([I]1a) is widely used in clinical single photon emission computed tomography (SPECT) imaging as a DAT imaging agent. To develop more metabolically stable DAT radioligands for accurate imaging, this work compared two novel deuterated tropane derivatives ([I]1c-d) with non-deuterated tropane derivatives ([I]1a-b). [I]1a-d were obtained in high radiochemical purity (RCP) above 99 % with molar activities of 7.0-10.0 GBq/μmol. The [I]1a and [I]1c exhibited relatively higher affinity to DAT (K: 2.0-3.12 nM) than [I]1b and [I]1d. Biodistribution results showed that [I]1c consistently exhibited a higher ratio of the target to non-target (striatum/cerebellum) than [I]1a. Furthermore, metabolism studies indicated that the in vivo metabolic stability of [I]1c was superior to that of [I]1a. Ex vivo autoradiography showed that [I]1c selectively localized on DAT-rich striatal regions and the specific signal could be blocked by DAT inhibitor. These results indicated that [I]1c might be a potential probe for DAT SPECT imaging in the brain.