Quantification of pituitary 5-HT_1B receptors with positron emission tomography: Negligible specific binding despite...

While Positron Emission Tomography (PET) images with the 5-HT_1B receptor specific radioligand [¹¹C]AZ10419369 show pronounced uptake in the pituitary region, and experimental studies support 5-HT_1B receptor involvement in pituitary hormonal release, this uptake remains unquantified. In the present study we applied invasive and non-invasive models to evaluate pituitary 5-HT_1B receptor binding. Ten subjects underwent PET with [¹¹C]AZ10419369, of which six participated in three additional PET-examinations after pretreatment with increasing doses of the 5-HT_1B receptor antagonist AZD3783. While [¹¹C]AZ10419369 binding in the brain displayed dose-dependent reductions after AZD3783, no dose-dependent inhibition of binding was observed for the pituitary. Distribution volume ratios were plotted against occupancy values to graphically estimate regional differences in non-displaceable binding, thereby allowing for estimation of BP_ND in extracerebral regions. Using this method, baseline pituitary BP_ND appears to be negligible, implying that most of the pituitary [¹¹C]AZ10419369 uptake is comprised of free or nonspecifically bound radioligand. Our findings highlight potential pitfalls when assuming that conspicuous regional radioligand uptake indicates presence of specific binding.