Simplified quantification of 5-HT2A receptors in the human brain with [11C]MDL 100,907 PET and non-invasive kinetic analyses.
BACKGROUND: [(11)C]MDL100,907 is a promising positron emission tomography (PET) ligand for 5-HT(2A) receptor quantification in vivo. Studies suggest that [(11)C]MDL100,907 PET may be quantified by non-invasive reference tissue analyses using cerebellum as reference region. We systematically investig...
| Main Authors: | , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
2010
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| _version_ | 1826296933193351168 |
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| author | Meyer, P Bhagwagar, Z Cowen, P Cunningham, V Grasby, P Hinz, R |
| author_facet | Meyer, P Bhagwagar, Z Cowen, P Cunningham, V Grasby, P Hinz, R |
| author_sort | Meyer, P |
| collection | OXFORD |
| description | BACKGROUND: [(11)C]MDL100,907 is a promising positron emission tomography (PET) ligand for 5-HT(2A) receptor quantification in vivo. Studies suggest that [(11)C]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 [(11)C]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 (BP(ND)) 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 BP(ND) 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 BP(ND), which were highly correlated with 2TCM analyses (R(2)>or=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)>or=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 BP(ND) (-26+/-22%; R(2)>or=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 [(11)C]MDL100,907 PET studies, yielding estimates of 5-HT(2A) receptor availability and changes that are highly correlated with results from invasive 2TCM analyses. This should greatly enhance the applicability of 5-HT(2A) receptor PET studies. |
| first_indexed | 2024-03-07T04:23:56Z |
| format | Journal article |
| id | oxford-uuid:cbfa3aac-f865-47be-a5f3-c6f2f19624ac |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:23:56Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:cbfa3aac-f865-47be-a5f3-c6f2f19624ac2022-03-27T07:18:33ZSimplified quantification of 5-HT2A receptors in the human brain with [11C]MDL 100,907 PET and non-invasive kinetic analyses.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cbfa3aac-f865-47be-a5f3-c6f2f19624acEnglishSymplectic Elements at Oxford2010Meyer, PBhagwagar, ZCowen, PCunningham, VGrasby, PHinz, RBACKGROUND: [(11)C]MDL100,907 is a promising positron emission tomography (PET) ligand for 5-HT(2A) receptor quantification in vivo. Studies suggest that [(11)C]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 [(11)C]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 (BP(ND)) 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 BP(ND) 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 BP(ND), which were highly correlated with 2TCM analyses (R(2)>or=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)>or=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 BP(ND) (-26+/-22%; R(2)>or=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 [(11)C]MDL100,907 PET studies, yielding estimates of 5-HT(2A) receptor availability and changes that are highly correlated with results from invasive 2TCM analyses. This should greatly enhance the applicability of 5-HT(2A) receptor PET studies. |
| spellingShingle | Meyer, P Bhagwagar, Z Cowen, P Cunningham, V Grasby, P Hinz, R Simplified quantification of 5-HT2A receptors in the human brain with [11C]MDL 100,907 PET and non-invasive kinetic analyses. |
| title | Simplified quantification of 5-HT2A receptors in the human brain with [11C]MDL 100,907 PET and non-invasive kinetic analyses. |
| title_full | Simplified quantification of 5-HT2A receptors in the human brain with [11C]MDL 100,907 PET and non-invasive kinetic analyses. |
| title_fullStr | Simplified quantification of 5-HT2A receptors in the human brain with [11C]MDL 100,907 PET and non-invasive kinetic analyses. |
| title_full_unstemmed | Simplified quantification of 5-HT2A receptors in the human brain with [11C]MDL 100,907 PET and non-invasive kinetic analyses. |
| title_short | Simplified quantification of 5-HT2A receptors in the human brain with [11C]MDL 100,907 PET and non-invasive kinetic analyses. |
| title_sort | simplified quantification of 5 ht2a receptors in the human brain with 11c mdl 100 907 pet and non invasive kinetic analyses |
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