PuSH - Publikationsserver des Helmholtz Zentrums München: Drug occupancy assessment at the glucose-dependent insulinotropic polypeptide (GIP) receptor by positron emission tomography.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Eriksson, O.* ; Velikyan, I.* ; Haack, T.* ; Bossart, M.* ; Evers, A.* ; Lorenz, K.* ; Laitinen, I.* ; Larsen, P.J.* ; Plettenburg, O. ; Johansson, L.* ; Pierrou, S.* ; Wagner, M.*

Drug occupancy assessment at the glucose-dependent insulinotropic polypeptide (GIP) receptor by positron emission tomography.

Diabetes 70, 842-853 (2021)

Verlagsversion

DOI

PMC

	Closed

Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

Abstract
Metriken
Zusatzinfos

Targeting of the Glucose-dependent Insulinotropic Polypeptide receptor GIPR is an emerging strategy in anti-diabetic 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 with Gallium-68. The resulting PET tracer [⁶⁸Ga]S02-GIP-T4 was evaluated for affinity and specificity to human GIPR (huGIPR). The in vivo GIPR binding of [⁶⁸Ga]S02-GIP-T4, as well as the occupancy of a drug candidate with GIPR activity, was assessed in non-human primates (NHP) by PET.[⁶⁸Ga]S02-GIP-T4 bound with nanomolar affinity and high selectivity to huGIPR in overexpressing cells. In vivo pancreatic binding in NHP could be dose dependently inhibited by co-injection of unlabelled S02-GIP-T4. Finally, subcutaneous pre-treatment with a high dose of a drug candidate with GIPR activity led to a decreased pancreatic binding of [⁶⁸Ga]S02-GIP-T4, corresponding to a GIPR drug occupancy of almost 90%. [⁶⁸Ga]S02-GIP-T4 demonstrated a safe dosimetric profile, allowing for repeated studies in humans. In conclusion, [⁶⁸Ga]S02-GIP-T4 is a novel PET biomarker for safe, non-invasive, and quantitative assessment of GIPR target distribution and drug occupancy.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Scopus
Cited By

Altmetric

9.461

0.000