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Simultaneous SPECT Studies of Pre- and Postsynaptic Dopamine Binding Sites in Baboons

Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania

Correspondence: For correspondence or reprints contact: Stefan H.J. Dresel, MD, Department of Radiology, University of Pennsylvania, 3700 Market St., Room 305, Philadelphia, PA 19104.

ABSTRACT

The central nervous system dopamine transporters (DAT5) and dopamine D₂/D₃ receptors are implicated in a variety of neurological disorders. Both sites are also targets for drug treatment. With the successful development of [^99mTc]TRODAT-1, single isotope imaging studies using this ligand for DAT imaging can be complemented by additional use of ¹²³I-labeled D₂/D₃ 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) [^99mTc]-TRODAT-1 (technetium, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl) amino]ethyl]-amino]ethanethiolato (3-)]- oxo-[1R-(exo-exo)]) and 185 MBq (5 mCi) [¹²³l]iodobenzamide or [¹²³l]iodobenzofuran. SPECT data were acquired by a triple-head gamma camera equipped with ultra-high-resolution fanbeam collimators (scan duration = 210 min). Two sets of SPECT data were obtained using energy windows of 15% centered on 140 keV for ^99mTc and 10% asymmetric with a lower bound at 159 keV for ¹²³l. After coregistration with MRI, region-of-interest analysis was performed using predefined templates from coregistered MRI. In blocking studies, baboons were pretreated with N-methyl-2ß-carbomethoxy-3ß-(4-fluorophenyl)tropane (CFT, 14 mg) or raclopride (14 mg) to block DAT or D₂/D₃ binding site, respectively. Results: Image quality of dual-isotope studies was similar to that obtained from single-isotope studies. 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 the first example that clearly demonstrates the feasibility of simultaneous imaging of both pre-and postsynaptic sites of the dopaminergic system in baboons with dual-isotope SPECT studies. With or without corrections for cross-contamination of ¹²³l into the ^99mTc window, striatum-to-cerebellum ratios (target-to-nontarget) of dual-isotope experiments did not differ significantly from single-isotope experiments. This method may be a valuable and cost-effective tool for gaining comprehensive information about the dopaminergic system in one SPECT imaging session.

Key Words: dopamine transporters • dopamine D₂/D₃ receptors • SPECT imaging • dual-isotope studies

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