An article recently published in the Journal of Cerebral Blood Flow & Metabolism describes the development of new models for analysing data from Positron Emission Tomography (PET) displacement studies. This is an alternative study design for target engagement in which treatment is administered during one ongoing PET scan.
Researchers from Copenhagen University Hospital, Amsterdam UMC, Columbia University, and Antaros Medical have developed this framework of models and validated it using PET displacement data.
PET target engagement studies are intended to verify that a drug is binding to its target. Traditionally these studies are designed such that a subject will have a baseline scan before treatment, then the treatment will be administered, and there will be at least one follow-up scan taken. During all scans, the amount of radiotracer uptake is measured and then the difference observed between the scans is used to estimate occupancy, the proportion of targets occupied by the treatment.
An alternative approach is to administer the treatment during the course of a single PET scan. The drug will then displace the radiotracer from the target, causing a change in the measured PET signal. The displacement study design has several advantages over the traditional approach; the subject is exposed to only one dose of ionising radiation and as each patient will need only one PET scan, this can greatly reduce costs. And most importantly, requiring only one scan can reduce the risk of unwanted variance and thereby enable a more reliable estimation.
As the models used to analyse traditional PET studies are not suitable for displacement studies, new models need to be developed and adapted. The paper demonstrates that the developed models could make performing PET displacement studies a viable alternative to traditional PET occupancy studies.
Title: Kinetic models for estimating occupancy from single-scan PET displacement studies
Authors: Laurell GL, Plavén-Sigray P, Johansen A, Raval NR, Nasser A, Aabye Madsen C, Madsen J, Hansen HD, Donovan LL, Knudsen GM, Lammertsma AA, Ogden RT, Svarer C, Schain M
Find the publication here.