Kinetic models for estimating occupancy from single-scan PET displacement studies

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Gjertrud Louise Laurell
  • Pontus Plavén-Sigray
  • Annette Johansen
  • Nakul Ravi Raval
  • Arafat Nasser
  • Madsen, Clara Marianne Aabye
  • Jacob Madsen
  • Hanne Demant Hansen
  • Lene Lundgaard Donovan
  • Knudsen, Gitte Moos
  • Adriaan A. Lammertsma
  • R. Todd Ogden
  • Claus Svarer
  • Martin Schain
The traditional design of PET target engagement studies is based on a baseline scan and one or more scans after drug administration. We here evaluate an alternative design in which the drug is administered during an on-going scan (i.e., a displacement study). This approach results both in lower radiation exposure and lower costs. Existing kinetic models assume steady state. This condition is not present during a drug displacement and consequently, our aim here was to develop kinetic models for analysing PET displacement data. We modified existing compartment models to accommodate a time-variant increase in occupancy following the pharmacological in-scan intervention. Since this implies the use of differential equations that cannot be solved analytically, we developed instead one approximate and one numerical solution. Through simulations, we show that if the occupancy is relatively high, it can be estimated without bias and with good accuracy. The models were applied to PET data from six pigs where [11C]UCB-J was displaced by intravenous brivaracetam. The dose-occupancy relationship estimated from these scans showed good agreement with occupancies calculated with Lassen plot applied to baseline-block scans of two pigs. In summary, the proposed models provide a framework to determine target occupancy from a single displacement scan.
OriginalsprogEngelsk
TidsskriftJournal of Cerebral Blood Flow and Metabolism
Vol/bind43
Udgave nummer9
Sider (fra-til)1544-1556
Antal sider13
ISSN0271-678X
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 796759. GLL was supported by Rigshospitalet’s Research Council (R197-A8956). PPS was supported by the Swedish Society for Medicine and the Lundbeck Foundation (R303-2018-3263). AJ was supported by The Independent Research Fund Denmark. NRR was funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 813528. HDH was supported by the Lundbeck Foundation (R293-2018-738). RTO and AAL were supported by visiting professorships from the Lundbeck Foundation (R317-2019-787 and R290-2018-756). Acknowledgements

Publisher Copyright:
© The Author(s) 2023.

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