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Title
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Kinetic modelling and test-retest reproducibility for the dopamine D₁R radioligand [¹¹C]SCH23390 in healthy and diseased mice
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Author
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Abstract
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| Purpose Our aim in this study was to compare different non-invasive pharmacokinetic models and assess test-retest reproducibility of the radioligand [C-11]SCH23390 for the quantification of dopamine D-1-like receptor (D1R) in both wild-type (WT) mice and heterozygous (HET) Q175DN mice as Huntington's disease (HD) model. Procedures Adult WT (n = 9) and HET (n = 14) mice underwent a 90-min [C-11]SCH23390 positron emission tomography (PET) scan followed by computed tomography (CT) to evaluate the pharmacokinetic modelling in healthy and diseased conditions. Additionally, 5 WT mice and 7 HET animals received a second [C-11]SCH23390 PET scan for test-retest reproducibility. Parallel assessment of the simplified reference tissue model (SRTM), the multilinear reference tissue model (MRTM) and the Logan reference tissue model (Logan Ref) using the striatum as a receptor-rich region and the cerebellum as a receptor-free (reference) region was performed to define the most suitable method for regional- and voxel-based quantification of the binding potential (BPND). Finally, standardised uptake value ratio (SUVR-1) was assessed as a potential simplified measurement. Results For all models, we measured a significant decline in dopamine D1R density (e.g. SRTM = - 38.5 +/- 5.0 %, p < 0.0001) in HET mice compared to WT littermates. Shortening the 90-min scan duration resulted in large underestimation of striatal BPND in both WT mice (SRTM 60 min: - 17.7 +/- 2.8 %, p = 0.0078) and diseased HET (SRTM 60 min: - 13.1 +/- 4.1 %, p = 0.0001). Striatal BPND measurements were very reproducible with an average test-retest variability below 5 % when using both MRTM and SRTM. Parametric BPND maps generated with SRTM were highly reliable, showing nearly perfect agreement to the regional analysis (r(2) = 0.99, p < 0.0001). Finally, SRTM provided the most accurate estimate for relative tracer delivery R-1 with both regional- and voxel-based analyses. SUVR-1 at different time intervals were not sufficiently reliable when compared to BPND (r(2) < 0.66). Conclusions Ninety-minute acquisition and the use of SRTM for pharmacokinetic modelling is recommended. [C-11]SCH23390 PET imaging demonstrates optimal characteristics for the study of dopamine D1R density in models of psychiatric and neurological disorders as exemplified in the Q175DN mouse model of HD. |
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Language
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English
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Source (journal)
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Molecular imaging and biology. - New York, N.Y., 2002, currens
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Publication
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New york
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Springer
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2021
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ISSN
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1536-1632
[print]
1860-2002
[online]
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DOI
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10.1007/S11307-020-01561-1
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Volume/pages
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23
:2
(2021)
, p. 208-219
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ISI
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000588591000001
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Pubmed ID
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33179158
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Full text (Publisher's DOI)
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Full text (open access)
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