While Positron Emission Tomography (PET) images with the 5-HT 1B receptor specific radioligand 11 CAZ10419369 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 11 CAZ10419369, of which six participated in three additional PET-examinations after pretreatment with increasing doses of the 5-HT 1B receptor antagonist AZD3783. While 11 CAZ10419369 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 11 CAZ10419369 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.
Gärde et al. (Sun,) studied this question.