Mapping α₂ adrenoceptors of the human brain with¹¹C-yohimbine

A previous study from this laboratory suggested that ¹¹C-yohimbine, a selective α₂-adrenoceptor antagonist, is an appropriate ligand for PET of α₂ adrenoceptors that passes readily from blood to brain tissue in pigs but not in rodents. To test usefulness in humans, we determined blood-brain clearances, volumes of distribution, and receptor availability by means of PET with ¹¹C-yohimbine in healthy male adults. Methods: We recorded the distribution of ¹¹C-yohimbine with 90-min dynamic PET and sampled arterial blood to measure intact ¹¹C-yohimbine in plasma. For analysis, we coregistered PET images to individual MR images and automatically identified 27 volumes of interest. We used 1-tissue-compartment graphical analysis with 6 linearized solutions of the fundamental binding equation, with the metabolite-corrected arterial plasma curves as input function, to estimate the kinetic parameters of ¹¹C-yohimbine. With the lowest steady-state distribution volume (V_T), determined in the corpus callosum, we calculated the binding potential (receptor availability) of the radioligand in other regions. Results: The linear regressions yielded similar estimates of the kinetic parameters. The cortical values of V_T ranged from 0.82 mL cm^-3 in the right frontal cortex to 0.46 mL cm^-3 in the corpus callosum, with intermediate V_T values in subcortical structures. Binding potentials averaged 0.6-0.8 in the cortex and 0.2-0.5 in subcortical regions. Conclusion: The maps of ¹¹C-yohimbine binding to α₂ adrenoceptors in human brain had the highest values in cortical areas and hippocampus, with moderate values in subcortical structures, as found also in vitro. The results confirm the usefulness of the tracer ¹¹C-yohimbine for mapping α₂ adrenoceptors in human brain in vivo.