Abstract
Background: [C-11]MDL100,907 is a promising positron emission tomography (PET) ligand for 5-HT2A receptor quantification in vivo. Studies suggest that [C-11]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 [C-11]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 (R-2 >= 0.86) although with negative bias (-29 +/- 27% at baseline across all ROI). NIGA was less biased (-19 +/- 16%) and better correlated with 2TCM (R-2 >= 0.93). Regarding Occ, NIGA and SRTM2/MRTM2 showed Comparable mean biases (-11 +/- 27% vs. -7 +/- 47%) but correlation with 2TCM was higher for NIGA (R-2 = 0.90 vs. 0.77). NIGA parametric maps (analysed using identical ROI) resulted in moderate bias in BPND (-26 +/- 22%; R-2 >= 0.88) and Occ (-17 +/- 36%: R-2 = 0.78). Estimates obtained from tissue ratios performed least favourably. Conclusions: NIGA is well suited for analysis of [C-11]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.
Original language | English |
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Pages (from-to) | 984-993 |
Number of pages | 10 |
Journal | Neuroimage |
Volume | 50 |
Issue number | 3 |
Early online date | 18 Jan 2010 |
DOIs | |
Publication status | Published - 15 Apr 2010 |
Keywords
- [C-11]MDL 100,907
- 5-HT2A receptor
- positron emission tomography
- tracer kinetic modelling
- reference region
- positron-emission-tomography
- graphical analysis method
- reference tissue model
- living human-brain
- serotonin receptors
- binding
- dopamine
- ligand
- neuroreceptor
- radioligand