DiabetesFeb 6, 2021

Measuring How a Drug Binds to the Glucose-Dependent Insulinotropic Polypeptide Receptor Using PET Scans

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 17, 2026

Abstract

[Ga]S02-GIP-T4 exhibited a GIPR drug occupancy of almost 90% in nonhuman primates.

The GIPR-selective peptide S02-GIP was successfully radiolabeled to create the PET tracer [Ga]S02-GIP-T4.
[Ga]S02-GIP-T4 showed nanomolar affinity and high specificity to human GIPR in laboratory tests.
In vivo studies indicated that pancreatic binding of [Ga]S02-GIP-T4 could be dose-dependently inhibited.
The PET biomarker [Ga]S02-GIP-T4 has a safe dosimetric profile, which may allow for repeated studies in humans.

Simplified

Targeting of the glucose-dependent insulinotropic polypeptide receptor (GIPR) is an emerging strategy in antidiabetic drug development. The aim of this study was to develop a positron emission tomography (PET) radioligand for the GIPR to enable the assessment of target distribution and drug target engagement in vivo. The GIPR-selective peptide S02-GIP was radiolabeled withGa. The resulting PET tracer [Ga]S02-GIP-T4 was evaluated for affinity and specificity to human GIPR (huGIPR). The in vivo GIPR binding of [Ga]S02-GIP-T4 as well as the occupancy of a drug candidate with GIPR activity were assessed in nonhuman primates (NHPs) by PET. [Ga]S02-GIP-T4 bound with nanomolar affinity and high selectivity to huGIPR in overexpressing cells. In vivo, pancreatic binding in NHPs could be dose-dependently inhibited by coinjection of unlabeled S02-GIP-T4. Finally, subcutaneous pretreatment with a high dose of a drug candidate with GIPR activity led to a decreased pancreatic binding of [Ga]S02-GIP-T4, corresponding to a GIPR drug occupancy of almost 90%. [Ga]S02-GIP-T4 demonstrated a safe dosimetric profile, allowing for repeated studies in humans. In conclusion, [Ga]S02-GIP-T4 is a novel PET biomarker for safe, noninvasive, and quantitative assessment of GIPR target distribution and drug occupancy. 68 68 68 68 68 68 68

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Measuring How a Drug Binds to the Glucose-Dependent Insulinotropic Polypeptide Receptor Using PET Scans

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