| Autor: |
Halff, Els, Natesan, Sridhar, Bonsall, David R., Veronese, Mattia, Garcia-Hidalgo, Anna, Kokkinou, Michelle, Tang, Sac-Pham, Riggall , Laura, Gunn, Roger, Irvine, Elaine, Withers, Dominic, Wells, Lisa, Howes, Oliver |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Zdroj: |
Halff, E, Natesan, S, Bonsall, D R, Veronese, M, Garcia-Hidalgo, A, Kokkinou, M, Tang, S-P, Riggall, L, Gunn, R, Irvine, E, Withers, D, Wells, L & Howes, O 2022, ' Evaluation of intraperitoneal [ 18 F]-FDOPA administration for micro-PET imaging in mice and assessment of the effect of sub-chronic ketamine dosing on dopamine synthesis capacity ', Molecular Imaging . |
| Popis: |
Positron emission tomography (PET) using the radiotracer [18F]-FDOPA provides a tool for studying brain dopamine synthesis capacity in animals and humans. We have previously standardised a micro-PET methodology in mice by intravenously administering [18F]-FDOPA via jugular vein cannulation, and assessment of striatal dopamine synthesis capacity, indexed as the influx rate constant KiMod of [18F]-FDOPA, using extended graphical Patlak analysis with the cerebellum as a reference region. This enables a direct comparison between preclinical and clinical output values. However, chronic intravenous catheters are technically difficult to maintain for longitudinal studies. Hence, in this study, intraperitoneal administration of [18F]-FDOPA was evaluated as a less invasive alternative that facilitates longitudinal imaging. Our experiments comprised the following assessments: (i) comparison of [18F]-FDOPA uptake between intravenous and intraperitoneal radiotracer administration and optimisation of the time window used for extended Patlak analysis, (ii) comparison of KiMod in a within-subject design of both administration routes, (iii) test-retest evaluation of KiMod in a within-subject design of intraperitoneal radiotracer administration, and (iv) validation of KiMod estimates by comparing the two administration routes in a mouse model of hyperdopaminergia induced by sub-chronic ketamine. Our results demonstrate that intraperitoneal [18F]-FDOPA administration resulted in good brain uptake, with no significant effect of administration route on KiMod estimates (intraperitoneal: 0.024+0.0047 min-1, intravenous: 0.022+0.0041 min-1, p=0.42) and similar coefficient of variation (intraperitoneal: 19.6%; intravenous: 18.4%). The technique had a moderate test-retest validity (intraclass correlation coefficient, ICC=0.52, N=6), and thus supports longitudinal studies. Following sub-chronic ketamine administration, elevated KiMod as compared to control condition was measured with a large effect size for both methods (intraperitoneal: Cohen’s d=1.3; intravenous: Cohen’s d=0.9), providing further evidence that ketamine has lasting effects on the dopamine system, which could contribute to its therapeutic actions and/or abuse liability. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
