Positron emission tomography to assess drug occupancy at peripheral and central incretin receptors.

ABSTRACT:

Background

Incretin mimetics, especially dual/triple agonists, are effective for type 2 diabetes and obesity, though mechanisms remain unclear. This study applied PET using [⁶⁸Ga]Ga-DO3A-Exendin-4 and [⁶⁸Ga]S02-GIP-T4 to assess GLP-1R and GIPR occupancy of SAR441255 (a GLP-1R, GIPR, and GCGR agonist) and tirzepatide in pig pancreas and CNS.

Methods

In vitro binding assays on frozen HEK293 cell sections overexpressing human GLP-1R, GIPR, or GCGR assessed [⁶⁸Ga]Ga-DO3A-Exendin-4 specificity and competition with tirzepatide and SAR441255, and [⁶⁸Ga]S02-GIP-T4 with SAR441255. In vivo, the GLP-1R occupancy by SAR441255 and tirzepatide, and GIPR occupancy by SAR441255, was evaluated in healthy pigs using PET/CT initiated at tracer inject

SUBMITTER: Khalil A 

PROVIDER: S-EPMC12682123 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature