Dynamic imaging of striatal D2 receptors in mice using quad-HIDAC

HIDAC, offers submillimeter resolution in instrumental charac-terization experiments. The aim of this study was to establish the tomograph’s utility in a biologic application and to demon-strate the feasibility of rapid dynamic neuroreceptor imaging in mice. Methods: We used the well-established, high-affinity do-pamine D2 receptor PET ligand 18F-fallypride for imaging striatal D2 receptors in NMRI mice. Dynamic PET data were acquired using the quad-HIDAC tomograph and subject to 2 different kinetic modeling approaches. The cerebellum, a brain region devoid of D2 receptors, was chosen as a reference region for kinetic modeling. Results: The resolution of the quad-HIDAC camera allowed clear visualization of the left and right mouse striatum with high target-to-nontarget signal ratios. The sensi-tivity of the tomograph permitted the generation of time–activity curves with initial time frames of 120 s. PET experiments ac-quiring data for 150 min demonstrated that the binding potential of 18F-fallypride could be fitted robustly with both reference tissue models for scan durations of 40 min. Voxel-wise mod-eling resulted in parametric maps of high quality. The values for the binding potential in the striatum reached approximately 14, consistent with striatum-to-cerebellum ratios extracted from regional time–activity curves. Comparison of in vivo PET imag-ing results with ex vivo postmortem tissue sampling analyses indicated discrepancies in signal intensity, possibly resulting from scatter and random background in the cerebellum region of interest and leading to an overestimation of cerebellar activity concentrations and degradation of striatum-to-cerebellum ra-tios in PET experiments. Intraperitoneal injection of the unla-beled D2 receptor antagonist haloperidol 30 min before intrave-nous injection of 18F-fallypride blocked tracer accumulation in the striatum by 95%. Conclusion: The quad-HIDAC camera represents a powerful tool for future dynamic neuroreceptor PET studies in mice and rats under numerous pharmacologic or pathophysiologic conditions