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

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 [¹²³I]FP-CIT ([¹²³I]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 ([¹³¹I]1c-d) with non-deuterated tropane derivatives ([¹³¹I]1a-b). [¹³¹I]1a-d were obtained in high radiochemical purity (RCP) above 99 % with molar activities of 7.0-10.0 GBq/μmol. The [¹³¹I]1a and [¹³¹I]1c exhibited relatively higher affinity to DAT (K_i: 2.0-3.12 nM) than [¹³¹I]1b and [¹³¹I]1d. Biodistribution results showed that [¹³¹I]1c consistently exhibited a higher ratio of the target to non-target (striatum/cerebellum) than [¹³¹I]1a. Furthermore, metabolism studies indicated that the in vivo metabolic stability of [¹³¹I]1c was superior to that of [¹³¹I]1a. Ex vivo autoradiography showed that [¹³¹I]1c selectively localized on DAT-rich striatal regions and the specific signal could be blocked by DAT inhibitor. These results indicated that [¹³¹I]1c might be a potential probe for DAT SPECT imaging in the brain.