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In this study, we assess the impact of the reference tissue (frontal cortex, parietal cortex, cerebellum) on the magnitude of the binding potential obtained for the D2 receptor ligands [18F]N-methyl-benperidol and [123I]iodobenzamide in the rat striatum using dedicated small animal PET (“TierPET”), small animal SPECT (“TierSPECT”) or a conventional dual-head SPECT camera upgraded with multipinhole-collimators (“HiSPECT”). With all 3 cameras employed in our investigation, striatum-to-cerebellum ratios were consistently higher compared to striatum-to-cortex ratios. Moreover, frontal-cortex-to-cerebellum ratios tended to exceeded parietal-cortex-tocerebellum. Findings are in line with previous in vitro results, and show that quantitation of both striatal and cortical D2 receptor binding is feasible using small animal imaging devices including the novel HiSPECT. With HiSPECT, both striatum-to-cortex and striatum-to-cerebellum ratios of IBZM were higher compared to TierSPECT, which underlines the greater suitability of the higher resolving camera. Findings, moreover, imply that the reference tissue should be carefully chosen with respect to the intended investigation.

In the present study, the binding potential (BP) of the D2 receptor radioligand [18F]N-methyl-benperidol (FMB) was determined with in vivo saturation binding analysis using either cerebellum or parietal cortex as reference region. For the purpose of validation, BP additionally was determined in the same set of animals by computing the equilibrium ratios of the distribution volumes (V 3 ”). In a different set of animals, BP moreover was determined with in vitro storage phosphor autoradiography. With in vivo saturation binding analysis, the striatal BP as obtained with a cortical estimate for the free and non-specifically bound radioligand fell short of the BP as obtained with a cerebellar estimate by 70%. Similarly, with the equilibrium distribution volume method, the employment of a cortical REF led to a striatal V 3 ”, which was 30% lower than the V 3 ” obtained with a cerebellar REF. The BP determined with in vivo saturation binding analysis and a cerebellar REF provided a closer approximation to the autoradiographically obtained BP as the BP determined with in vivo saturation binding analysis and a cortical REF. Findings show that in vivo saturation binding analysis is a feasible approach to obtain receptor binding parameters if scanner characteristics or other technical limitations preclude the the kinetic modelling of binding data. However, caution should be exerted in choosing the reference tissue with regard to the intended investigation.