Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6036680 | NeuroImage | 2010 | 10 Pages |
Abstract
Background: [11C]MDL100,907 is a promising positron emission tomography (PET) ligand for 5-HT2A receptor quantification in vivo. Studies suggest that [11C]MDL100,907 PET may be quantified by non-invasive reference tissue analyses using cerebellum as reference region. We systematically investigated the validity of such analyses. Methods: Five healthy volunteers underwent [11C]MDL100,907 PET at baseline and after mirtazapine pre-treatment. Regional time-activity curves of 10 regions of interest (ROI) were analyzed for binding potential (BPND) and mirtazapine receptor occupancy (Occ) using: simplified reference tissue model (SRTM), multi-linear reference tissue model (MRTM), their two-parameter versions (SRTM2/MRTM2), non-invasive graphical analysis (NIGA) and a tissue activity concentration ratio. NIGA was also applied voxel-wise to generate BPND maps. These methods were compared with a two-tissue compartment model with arterial input function (2TCM) Results: SRTM and MRTM frequently failed to yield reliable results. SRTM2 and MRTM2 gave virtually identical estimates of BPND, which were highly correlated with 2TCM analyses (R2 â¥Â 0.86) although with negative bias (â 29 ± 27% at baseline across all ROI). NIGA was less biased (â 19 ± 16%) and better correlated with 2TCM (R2 â¥Â 0.93). Regarding Occ, NIGA and SRTM2/MRTM2 showed comparable mean biases (â 11 ± 27% vs. â 7 ± 47%) but correlation with 2TCM was higher for NIGA (R2 = 0.90 vs. 0.77). NIGA parametric maps (analysed using identical ROI) resulted in moderate bias in BPND (â 26 ± 22%; R2 â¥Â 0.88) and Occ (â 17 ± 36%; R2 = 0.78). Estimates obtained from tissue ratios performed least favourably. Conclusions: NIGA is well suited for analysis of [11C]MDL100,907 PET studies, yielding estimates of 5-HT2A receptor availability and changes that are highly correlated with results from invasive 2TCM analyses. This should greatly enhance the applicability of 5-HT2A receptor PET studies.
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Authors
Philipp T. Meyer, Zubin Bhagwagar, Philip J. Cowen, Vincent J. Cunningham, Paul M. Grasby, Rainer Hinz,