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Scientific result | Brain | Positron Emission Tomography | Pharmacology
Researchers at BioMaps (SHFJ) have succeeded in determining the interaction dynamics of buprenorphine, an opioid drug with a particularly complex pharmacology, with its brain receptors in vivo. To do so, they developed an original PET imaging approach based on the use of the radiolabeled molecule (11C-buprenorphine).
In the context of the development of new drugs, it is necessary to estimate the nature and degree of occupancy of their therapeutic targets (receptors) in humans. For this purpose, specific radio ligands of a given target are generally used and detected by PET (Positron Emission Tomography) imaging. However, this approach only gives an indirect view of the interaction of the drug with its target, because it is limited to a defined dose and time. It does not allow to directly assess the dynamics of the interaction of the studied drug with its receptors (association/dissociation kinetics, affinity for other targets...). In an article published in Neuropsychopharmacology, BioMaps* researchers have shown that it is possible to directly follow the interaction kinetics of buprenorphine (the active ingredient in Temgesic® and Subutex®) with its brain receptors (opioid receptors, ORs) thanks to an original PET approach, called " pharmacokinetic imaging ", which consists of using a radiolabelled analogue of the drug, here 11C-buprenorphine. They have thus established by in vivo PET imaging the binding profile of buprenorphine to the ORs (there are 3 subtypes of ORs: µ, d, k) and show in particular a strong and predominant affinity for the µ receptors, with a low reversibility of the binding on these receptors. More importantly, co-injection of 11C-buprenorphine with increasing doses of unlabeled buprenorphine allowed direct study of the cerebral kinetics and neuropharmacology of the molecule in different brain regions (Figure), with respect to a wide range of plasma concentrations encountered during its use as an analgesic or opioid replacement product.
This figure is part of the cover of the May 2021 issue of Neuropsychopharmacology.This original study, based on a "pharmacokinetic imaging" approach using a radiolabelled drug analogue administered here at pharmacological dose, allowed to decipher the particularly complex binding profile of buprenorphine to its receptors. This translational imaging approach is currently combined with measurements of buprenorphine effects (pharmacodynamics) in a clinical trial (SynchrOpioid protocol). Contact : Nicolas Tournier*UMR BioMaps (laboratoire d'Imagerie biomédicale multimodale Paris-Saclay, Université Paris-Saclay / CEA / CNRS / Inserm, Service Hospitalier Frédéric Joliot, institut Joliot, Orsay)
S. Auvity, S. Goutal, F. Caillé, D. Vodovar, A. Pruvost, C. Wimberley, C. Leroy, M. Tonietto, M. Bottlaender & N. Tournier. Pharmacokinetic neuroimaging to study the dose-related brain kinetics and target engagement of buprenorphine in vivo. Neuropsychopharmacology, vol 46, pages1220–1228 (2021) https://www.nature.com/articles/s41386-021-00976-w
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.