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  • Eriksson, OlofUppsala universitet,Science for Life Laboratory, SciLifeLab,Translationell avbildning med PET,Antaros Med AB, Uppsala, Sweden (författare)

Glucagonlike Peptide-1 Receptor Imaging in Individuals with Type 2 Diabetes

  • Artikel/kapitelEngelska2022

Förlag, utgivningsår, omfång ...

  • 2021-09-09
  • Society of Nuclear Medicine,2022
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-476182
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-476182URI
  • https://doi.org/10.2967/jnumed.121.262506DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • The glucagonlike peptide-1 receptor (GLP1R) is a gut hormone receptor, intricately linked to regulation of blood glucose homeostasis via several mechanisms. It is an established and emergent drug target in metabolic disease. The PET radioligand 68Ga-DO3A-VS-exendin4 (68Ga-exendin4) has the potential to enable longitudinal studies of GLP1R in the human pancreas.Methods: 68Ga-exendin4 PET/CT examinations were performed on overweight-to-obese individuals with type 2 diabetes (n = 13) as part of a larger target engagement study (NCT03350191). A scanning protocol was developed to optimize reproducibility (target amount of 0.5 MBq/kg [corresponding to peptide amount of <0.2 µg/kg], blood sampling, and tracer stability assessment). The pancreas and abdominal organs were segmented, and binding was correlated with clinical parameters.Results: Uptake of 68Ga-exendin4 in the pancreas, but not in other abdominal tissues, was high but variable between individuals. There was no evidence of self-blocking of GLP1R by the tracer in this protocol, despite the high potency of exendin4. The results showed that a full dynamic scan can be simplified to a short static scan, potentially increasing throughput and reducing patient discomfort. The 68Ga-exendin4 concentration in the pancreas (i.e., GLP1R density) correlated inversely with the age of the individual and tended to correlate positively with body mass index. However, the total GLP1R content in the pancreas did not.Conclusion: In summary, we present an optimized and simplified 68Ga-exendin4 scanning protocol to enable reproducible imaging of GLP1R in the pancreas. 68Ga-exendin4 PET may enable quantification of longitudinal changes in pancreatic GLP1R during the development of type 2 diabetes, as well as target engagement studies of novel glucagonlike peptide-1 agonists.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Velikyan, Irina,1966-Uppsala universitet,Translationell avbildning med PET,Akad Sjukhuset, Uppsala, Sweden(Swepub:uu)irinveli (författare)
  • Haack, TorstenSanofi, Integrated Drug Discovery, R&D Res Platform, Frankfurt, Germany. (författare)
  • Bossart, MartinSanofi, Integrated Drug Discovery, R&D Res Platform, Frankfurt, Germany. (författare)
  • Laitinen, IinaSanofi, Global Imaging, Frankfurt, Germany. (författare)
  • Larsen, Philip J.Sanofi, Diabet Res, Frankfurt, Germany. (författare)
  • Berglund, Jan ErikClin Trial Consultants AB, Uppsala, Sweden. (författare)
  • Antoni, GunnarUppsala universitet,Preparativ läkemedelskemi,Akad Sjukhuset, Uppsala, Sweden(Swepub:uu)gunnarat (författare)
  • Johansson, LarsAntaros Med AB, Uppsala, Sweden. (författare)
  • Pierrou, StefanAntaros Med AB, Uppsala, Sweden. (författare)
  • Tillner, JoachimSanofi, Translat Med, Frankfurt, Germany. (författare)
  • Wagner, MichaelSanofi, Integrated Drug Discovery, R&D Res Platform, Frankfurt, Germany. (författare)
  • Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Nuclear Medicine: Society of Nuclear Medicine63:5, s. 794-8000161-55051535-56672159-662X

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