In vitro and In vivo Assessment of Suitable Reference Region and Kinetic Modelling for the mGluR1 Radioligand [11C]ITDM in Mice.

摘要: This study aimed at investigating binding specificity, suitability of reference region-based kinetic modelling, and pharmacokinetics the metabotropic glutamate receptor 1 (mGluR1) radioligand [11C]ITDM in mice. We performed vivo blocking as well displacement during positron emission tomography (PET) imaging using specific mGluR1 antagonist YM-202074. Additionally, we assessed vitro [3H]ITDM two different doses As an alternative to region models, validated use a noninvasive image-derived input function (IDIF) compared arterial measured with invasive arteriovenous (AV) shunt population-based curve for radiometabolite correction characterized pharmacokinetic modelling mouse brain. Finally, also semi-quantitative approaches. In YM-202074 resulted decreased binding, ranging from − 35.8 ± 8.0 % pons − 65.8 ± 3.0 % thalamus. Displacement was markedly observed all tested regions. addition, could be blocked dose-dependent manner. The volume distribution (VT) based on IDIF (VT (IDIF)) showed excellent agreement VT values metabolite-corrected plasma regardless metabolite (r2 > 0.943, p   0.960, p < 0.0001). A minimum scan duration 80 min required proper parameter estimation. SUV not reliable (r2 = 0.379, p = 0.0011), unlike ratio function, which valid approach. No suitable identified strongly supported by evidence brain However, applying appropriate PET represents promising tool visualize