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OtherClinical Investigations (Human)

Imaging of the glucagon receptor in subjects with type 2 diabetes

Olof Eriksson, Irina Velikyan, Torsten Haack, Martin Bossart, Iina Laitinen, Philip J Larsen, Jan-Erik Berglund, Gunnar Antoni, Lars Johansson, Stefan Pierrou, Joachim Tillner and Michael Wagner
Journal of Nuclear Medicine October 2020, jnumed.118.213306; DOI: https://doi.org/10.2967/jnumed.118.213306
Olof Eriksson
1 Uppsala University, Sweden;
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Irina Velikyan
1 Uppsala University, Sweden;
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Torsten Haack
2 Sanofi;
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Martin Bossart
2 Sanofi;
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Iina Laitinen
2 Sanofi;
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Philip J Larsen
2 Sanofi;
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Jan-Erik Berglund
3 Clinical Trial Consultants AB;
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Gunnar Antoni
1 Uppsala University, Sweden;
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Lars Johansson
4 Antaros Medical AB
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Stefan Pierrou
4 Antaros Medical AB
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Joachim Tillner
2 Sanofi;
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Michael Wagner
2 Sanofi;
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Abstract

Rationale: 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 human. The Positron Emission Tomography (PET) radioligand 68Ga-DO3A-VS-Tuna-2 (68Ga-Tuna-2) was developed to yield a non-invasive imaging marker for GCGR target distribution and drug target engagement in humans. Methods: The biodistribution and dosimetry of 68Ga-Tuna-2 was assessed by PET/Computed Tomography (CT) in n = 13 individuals with Type 2 Diabetes (T2D) as part of a clinical study assessing the occupancy of dual GCGR/Glucagon Like Peptide-1 Receptor (GLP-1R) agonist SAR425899. Binding of 68Ga-Tuna-2 in liver and reference tissues was evaluated and correlated to biometrics (e.g. weight or BMI) or other biomarkers (e.g. plasma glucagon levels). Results: 68Ga-Tuna-2 binding was seen primarily in the liver, which is in line with the strong expression of GCGR on hepatocytes. Kidney demonstrated high excretion related retention, while all other tissue demonstrated rapid washout. The Standardized Uptake Value (SUV)55min uptake endpoint was sensitive to endogenous levels of glucagon. 68Ga-Tuna-2 exhibited a safe dosimetry profile, and no adverse events after intravenous administration. Conclusion: 68Ga-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.

  • Endocrine
  • Hepatology
  • Molecular Imaging
  • PET
  • glucagon
  • metabolic disease
  • obesity
  • type 2 diabetes
  • Copyright © 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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Journal of Nuclear Medicine: 62 (3)
Journal of Nuclear Medicine
Vol. 62, Issue 3
March 1, 2021
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Imaging of the glucagon receptor in subjects with type 2 diabetes
Olof Eriksson, Irina Velikyan, Torsten Haack, Martin Bossart, Iina Laitinen, Philip J Larsen, Jan-Erik Berglund, Gunnar Antoni, Lars Johansson, Stefan Pierrou, Joachim Tillner, Michael Wagner
Journal of Nuclear Medicine Oct 2020, jnumed.118.213306; DOI: 10.2967/jnumed.118.213306

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Imaging of the glucagon receptor in subjects with type 2 diabetes
Olof Eriksson, Irina Velikyan, Torsten Haack, Martin Bossart, Iina Laitinen, Philip J Larsen, Jan-Erik Berglund, Gunnar Antoni, Lars Johansson, Stefan Pierrou, Joachim Tillner, Michael Wagner
Journal of Nuclear Medicine Oct 2020, jnumed.118.213306; DOI: 10.2967/jnumed.118.213306
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Keywords

  • Endocrine
  • Hepatology
  • molecular imaging
  • PET
  • glucagon
  • metabolic disease
  • obesity
  • type 2 diabetes
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