PET brain kinetics studies of 11C-ITMM and 11C-ITDM,radioprobes for metabotropic glutamate receptor type 1, in a nonhuman primate

摘要

The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed sup11/supC-labeled PET probes sup11/supC-ITMM and sup11/supC-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared sup11/supC-ITMM and sup11/supC-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with sup11/supC-ITDM than with sup11/supC-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VsubT/sub) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cmsup-3/sup for sup11/supC-ITMM and 3.6 mL∙cmsup-3/sup for sup11/supC-ITDM. By contrast, the VsubT/sub in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of sup11/supC-ITMM and sup11/supC-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that sup11/supC-ITDM may be superior to sup11/supC-ITMM as a PET probe for imaging of mGluR1, because regional VsubT/sub values in PET with sup11/supC-ITDM were higher than those of sup11/supC-ITMM. Clinical studies of sup11/supC-ITDM in humans will be necessary in the future.