Dataset Information
Kinetic Modelling and Test-Retest Reproducibility for the Dopamine D1R Radioligand [11C]SCH23390 in Healthy and Diseased Mice.
Ontology highlight
ABSTRACT: Purpose
Our aim in this study was to compare different non-invasive pharmacokinetic models and assess test-retest reproducibility of the radioligand [11C]SCH23390 for the quantification of dopamine D1-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 [11C]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 [11C]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?ND 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 (r2?=?0.99, p?1 with both regional- and voxel-based analyses. SUVR-1 at different time intervals were not sufficiently reliable when compared to BPND (r2?ConclusionsNinety-minute acquisition and the use of SRTM for pharmacokinetic modelling is recommended. [11C]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.
SUBMITTER: Bertoglio D
PROVIDER: S-EPMC7910372 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
Publications
Kinetic Modelling and Test-Retest Reproducibility for the Dopamine D<sub>1</sub>R Radioligand [<sup>11</sup>C]SCH23390 in Healthy and Diseased Mice.
Molecular imaging and biology 20201111 2
<h4>Purpose</h4>Our aim in this study was to compare different non-invasive pharmacokinetic models and assess test-retest reproducibility of the radioligand [<sup>11</sup>C]SCH23390 for the quantification of dopamine D<sub>1</sub>-like receptor (D<sub>1</sub>R) in both wild-type (WT) mice and heterozygous (HET) Q175DN mice as Huntington's disease (HD) model.<h4>Procedures</h4>Adult WT (n = 9) and HET (n = 14) mice underwent a 90-min [<sup>11</sup>C]SCH23390 positron emission tomography (PET) sca ...[more]