Imaging of the Glucagon Receptor in Subjects with Type 2 Diabetes

Eriksson, Olof (author): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för läkemedelskemi,Antaros Med AB, Uppsala

Velikyan, Irina, 1966- (author): Uppsala universitet,Institutionen för läkemedelskemi,Akad Sjukhuset, Uppsala, Sweden.

Haack, Torsten (author): Sanofi, Integrated Drug Discovery, R&D Res Platform, Frankfurt, Germany.

Bossart, Martin (author): Sanofi, Integrated Drug Discovery, R&D Res Platform, Frankfurt, Germany.

Larsen, Philip J. (author): Sanofi, Integrated Drug Discovery, R&D Res Platform, Frankfurt, Germany.

Antoni, Gunnar (author): Uppsala universitet,Institutionen för läkemedelskemi,Akad Sjukhuset, Uppsala, Sweden.

Wagner, Michael (author): Sanofi, Integrated Drug Discovery, R&D Res Platform, Frankfurt, Germany.

(creator_code:org_t)

2020-10-23
2021
English.
In: Journal of Nuclear Medicine. - : SOC NUCLEAR MEDICINE INC. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 62:6, s. 833-838

Related links:: https://jnm.snmjourn...; show more...; https://urn.kb.se/re...; https://doi.org/10.2...; show less...

Abstract Subject headings

Despite the importance of the glucagon receptor (GCGR) in disease and in pharmaceutical drug development, there is a lack of specific and sensitive biomarkers of its activation in humans. The PET radioligand Ga-68-DO3A-VS-Tuna-2 (Ga-68-Tuna-2) was developed to yield a noninvasive imaging marker for GCGR target distribution and drug target engagement in humans. Methods: The biodistribution and dosimetry of Ga-68-Tuna-2 was assessed by PET/CT in 13 individuals with type 2 diabetes as part of a clinical study assessing the occupancy of the dual GCGR/glucagon like peptide-1 receptor agonist SAR425899. Binding of Ga-68-Tuna-2 in liver and reference tissues was evaluated and correlated to biometrics (e.g., weight or body mass index) or other biomarkers (e.g., plasma glucagon levels). Results: Ga-68-Tuna-2 binding was seen primarily in the liver, which is in line with the strong expression of GCGR on hepatocytes. The kidneys demonstrated high excretion-related retention, whereas all other tissue demonstrated rapid washout. The SUV55 (min) (SUV during the last 10-min time frame, 50-60 min after administration) uptake endpoint was sensitive to endogenous levels of glucagon. Ga-68-Tuna-2 exhibited a safe dosimetry profile and no adverse events after intravenous administration. Conclusion: Ga-68-Tuna-2 can be used for safe and accurate assessment of the GCGR in human. It may serve as an important tool in understanding the in vivo pharmacology of novel drugs engaging the GCGR.

By the author/editor: Eriksson, Olof; Velikyan, Irina, ...; Haack, Torsten; Bossart, Martin; Laitinen, Iina; Larsen, Philip J ...; show more...; Berglund, Jan Er ...; Antoni, Gunnar; Johansson, Lars; Pierrou, Stefan; Tillner, Joachim; Wagner, Michael; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Radiology Nuclea ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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