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

Research output: Contribution to journalJournal articleResearchpeer-review

  • 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.

Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
Volume43
Issue number9
Pages (from-to)1544-1556
Number of pages13
ISSN0271-678X
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© The Author(s) 2023.

    Research areas

  • Displacement, drug occupancy, kinetic modelling, PET, synaptic density

ID: 369125716