Simultaneous SPECT studies of pre- and postsynaptic dopamine binding sitesin baboons

The central nervous system dopamine transporters (DATs) and dopamine D-2/D- 3, receptors are implicated in a variety of neurological disorders. Both si tes are also targets for drug treatment. With the successful development of [(TC)-T-99m]TRODAT-1 single-isotope imaging studies using this ligand for DAT imaging can be complemented by additional use of I-123-labeled D-2/D-3, receptor ligand co-injected to assess both pre- and postsynaptic sites of the dopaminergic system simultaneously. Methods: Twelve SPECT scans of the brain were obtained in two baboons after intravenous administration of 740 MBq (20 mCi) [Tc-99m]TRODAT-1 (technetium, [2-[[2-[[[3-(4-chlorophenyl)-8-m ethyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl) amino]ethyl]amin o]ethanethiolato (3-)]- oxo-[1R-(exo-exo)]) and 185 MBq (5 mCi) [I-123]iodo benzamide or [I-123]iodobenzofuran. SPECT data were acquired by a triple-he ad gamma camera equipped with ultra-high-resolution fanbeam collimators (sc an duration = 210 min). Two sets of SPECT data were obtained using energy w indows of 15% centered on 140 keV for Tc-99m and 10% asymmetric with a lowe r bound at 159 keV for I-123. After coregistration with MRI, region-of-inte rest analysis was performed using predefined templates from coregistered MR I. In blocking studies, baboons were pretreated with N-methyl-3 beta-carbom ethoxy-3 beta-(4-fluorophenyl)tropane (CFT, 14 mg) or raclopride (14 mg) to block DAT or D-2/D-3, binding site, respectively. Results: Image quality o f dual-isotope studies was similar to that obtained from single-isotope stu dies. When one site was blocked with CFT or raclopride, the binding of the respective ligand to the other site was not affected. Conclusion: This is t he first example that clearly demonstrates the feasibility of simultaneous imaging of both pre- and postsynaptic sites of the dopaminergic system in b aboons with dual-isotope SPECT studies. With or without corrections for cro ss-contamination of I-123 into the Tc-99m window, striatum-to-cerebellum ra tios (target-to-nontarget) of dual-isotope experiments did not differ signi ficantly from single-isotope experiments. This method may be a valuable and cost-effective tool for gaining comprehensive information about the dopami nergic system in one SPECT imaging session.