In vivo saturation binding analysis using small animal PET - the impact of the reference tissue on the binding potential of [18F]N-methyl-benperidol

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.