Quantification of pituitary 5-HT(1B) receptors with positron emission tomography: Negligible specific binding despite conspicuous uptake

利用正电子发射断层扫描定量分析垂体5-HT(1B)受体:尽管摄取显著,但特异性结合可忽略不计。

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Abstract

While Positron Emission Tomography (PET) images with the 5-HT(1B) receptor specific radioligand [(11)C]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 [(11)C]AZ10419369, of which six participated in three additional PET-examinations after pretreatment with increasing doses of the 5-HT(1B) receptor antagonist AZD3783. While [(11)C]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 [(11)C]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.

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