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Evaluation of Intraperitoneal [18F]-FDOPA Administration for Micro-PET Imaging in Mice and Assessment of the Effect of Subchronic Ketamine Dosing on Dopamine Synthesis Capacity.
Halff, Els F; Natesan, Sridhar; Bonsall, David R; Veronese, Mattia; Garcia-Hidalgo, Anna; Kokkinou, Michelle; Tang, Sac-Pham; Riggall, Laura J; Gunn, Roger N; Irvine, Elaine E; Withers, Dominic J; Wells, Lisa A; Howes, Oliver D.
Afiliação
  • Halff EF; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Natesan S; Psychiatric Imaging Group, MRC London Institute of Medical Sciences, London, UK.
  • Bonsall DR; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Veronese M; Psychiatric Imaging Group, MRC London Institute of Medical Sciences, London, UK.
  • Garcia-Hidalgo A; Psychiatric Imaging Group, MRC London Institute of Medical Sciences, London, UK.
  • Kokkinou M; Invicro, Burlington Danes, Hammersmith Hospital, London, UK.
  • Tang SP; Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Riggall LJ; Department of Information Engineering, University of Padua, Italy.
  • Gunn RN; Psychiatric Imaging Group, MRC London Institute of Medical Sciences, London, UK.
  • Irvine EE; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
  • Withers DJ; Psychiatric Imaging Group, MRC London Institute of Medical Sciences, London, UK.
  • Wells LA; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
  • Howes OD; Invicro, Burlington Danes, Hammersmith Hospital, London, UK.
Mol Imaging ; 2022: 4419221, 2022.
Article em En | MEDLINE | ID: mdl-36721730
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 K i Mod of [18F]-FDOPA, using an 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 Ki Mod in a within-subject design of both administration routes, (iii) test-retest evaluation of Ki Mod in a within-subject design of intraperitoneal radiotracer administration, and (iv) validation of Ki Mod estimates by comparing the two administration routes in a mouse model of hyperdopaminergia induced by subchronic ketamine. Our results demonstrate that intraperitoneal [18F]-FDOPA administration resulted in good brain uptake, with no significant effect of administration route on Ki Mod 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 subchronic ketamine administration, elevated K i Mod 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dopamina / Ketamina Tipo de estudo: Observational_studies Limite: Animals / Humans Idioma: En Revista: Mol Imaging Assunto da revista: DIAGNOSTICO POR IMAGEM Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dopamina / Ketamina Tipo de estudo: Observational_studies Limite: Animals / Humans Idioma: En Revista: Mol Imaging Assunto da revista: DIAGNOSTICO POR IMAGEM Ano de publicação: 2022 Tipo de documento: Article