Dynamic imaging of striatal D2 receptors in mice using quad-HIDAC PET.
The novel, dedicated small animal PET tomograph, quad-HIDAC, offers submillimeter resolution in instrumental characterization experiments. The aim of this study was to establish the tomograph's utility in a biologic application and to demonstrate the feasibility of rapid dynamic neuroreceptor imaging in mice.


METHODS
We used the well-established, high-affinity dopamine D(2) receptor PET ligand (18)F-fallypride for imaging striatal D(2) 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 D(2) 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 sensitivity of the tomograph permitted the generation of time-activity curves with initial time frames of 120 s. PET experiments acquiring data for 150 min demonstrated that the binding potential of (18)F-fallypride could be fitted robustly with both reference tissue models for scan durations of >or=40 min. Voxel-wise modeling 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 imaging 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 ratios in PET experiments. Intraperitoneal injection of the unlabeled D(2) receptor antagonist haloperidol 30 min before intravenous injection of (18)F-fallypride blocked tracer accumulation in the striatum by >95%.


CONCLUSIONS
The quad-HIDAC camera represents a powerful tool for future dynamic neuroreceptor PET studies in mice and rats under numerous pharmacologic or pathophysiologic conditions.
Honer
Michael
M
Center for Radiopharmaceutical Science, Paul Scherrer Institute, Villigen, Switzerland. michael.honer@psi.ch
Brühlmeier
Matthias
M
Missimer
John
J
Schubiger
August P
AP
Ametamey
Simon M
SM
D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics*; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019544:Equipment Failure Analysis; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000295:instrumentation* / Q000379:methods*
D001549:Benzamides; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2