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
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 asses...
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SAGE Publishing
2022-01-01
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| Series: | Molecular Imaging |
| Online Access: | http://dx.doi.org/10.1155/2022/4419221 |
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| author | Els F. Halff Sridhar Natesan David R. Bonsall Mattia Veronese Anna Garcia-Hidalgo Michelle Kokkinou Sac-Pham Tang Laura J. Riggall Roger N. Gunn Elaine E. Irvine Dominic J. Withers Lisa A. Wells Oliver D. Howes |
| author_facet | Els F. Halff Sridhar Natesan David R. Bonsall Mattia Veronese Anna Garcia-Hidalgo Michelle Kokkinou Sac-Pham Tang Laura J. Riggall Roger N. Gunn Elaine E. Irvine Dominic J. Withers Lisa A. Wells Oliver D. Howes |
| author_sort | Els F. Halff |
| collection | DOAJ |
| description | 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 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 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 subchronic 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 subchronic 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. |
| format | Article |
| id | doaj-art-f768fa347d054483bb676f5799b52e6f |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | SAGE Publishing |
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| series | Molecular Imaging |
| spelling | doaj-art-f768fa347d054483bb676f5799b52e6f2025-01-02T22:37:17ZengSAGE PublishingMolecular Imaging1536-01212022-01-01202210.1155/2022/4419221Evaluation of Intraperitoneal [18F]-FDOPA Administration for Micro-PET Imaging in Mice and Assessment of the Effect of Subchronic Ketamine Dosing on Dopamine Synthesis CapacityEls F. Halff0Sridhar Natesan1David R. Bonsall2Mattia Veronese3Anna Garcia-Hidalgo4Michelle Kokkinou5Sac-Pham Tang6Laura J. Riggall7Roger N. Gunn8Elaine E. Irvine9Dominic J. Withers10Lisa A. Wells11Oliver D. Howes12Institute of PsychiatryInstitute of PsychiatryPsychiatric Imaging GroupDepartment of NeuroimagingPsychiatric Imaging GroupPsychiatric Imaging GroupInvicroPsychiatric Imaging GroupInvicroInstitute of Clinical SciencesInstitute of Clinical SciencesInvicroInstitute of PsychiatryPositron 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 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 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 subchronic 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 subchronic 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.http://dx.doi.org/10.1155/2022/4419221 |
| spellingShingle | Els F. Halff Sridhar Natesan David R. Bonsall Mattia Veronese Anna Garcia-Hidalgo Michelle Kokkinou Sac-Pham Tang Laura J. Riggall Roger N. Gunn Elaine E. Irvine Dominic J. Withers Lisa A. Wells Oliver D. Howes 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 Molecular Imaging |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://dx.doi.org/10.1155/2022/4419221 |
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