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Positron emission tomography imaging of the glucagon-like peptide-1 receptor in healthy and streptozotocin-induced diabetic pigs

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Abstract

Purpose

The glucagon-like peptide-1 receptor (GLP-1R) has been proposed as a target for molecular imaging of beta cells. The feasibility of non-invasive imaging and quantification of GLP-1R in pancreas using the positron emission tomography (PET) tracer [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 in non-diabetic and streptozotocin (STZ)–induced diabetic pigs treated with insulin was investigated.

Methods

Non-diabetic (n = 4) and STZ-induced diabetic pigs (n = 3) from the same litter were examined. Development of diabetes was confirmed by blood glucose values, clinical examinations and insulin staining of pancreatic sections post mortem. Tissue perfusion in the pancreas and kidneys was evaluated by [15O]water PET/computed tomography (CT) scans. The in vivo receptor specificity of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 was assessed by administration of either tracer alone or by competition with 3–6.5 μg/kg of Exendin-4. Volume of distribution and occupancy in the pancreas were quantified with a single tissue compartment model.

Results

[15O]water PET/CT examinations showed reduced perfusion in the pancreas and kidneys in diabetic pigs. [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 uptake in the pancreas of both non-diabetic and diabetic pigs was almost completely abolished by co-injection of unlabeled Exendin-4 peptide. [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 uptake did not differ between non-diabetic and diabetic pigs. In all animals, administration of the tracer resulted in an immediate increase in the heart rate (HR).

Conclusion

Pancreatic uptake of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 was not reduced by destruction of beta cells in STZ-induced diabetic pigs.

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Acknowledgments

The excellent technical assistance by Dr. Sergio Estrada and Veronika Asplund is much appreciated. This study was supported by grants from the Swedish Research Council Formas (22120071090, VR K2011-65X-12219-15-6), the Nordic Insulin Fund, the Ernfors Family Fund, Barndiabetesfonden, the Swedish Diabetes Association, the Juvenile Diabetes Foundation International and Tore Nilsson’s Foundation for Medical Research. OK’s position is supported by the National Institutes of Health (2U01AI065192-06) and OE’s position is supported by EXODIAB (Excellence of Diabetes Research in Sweden).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden

    Lovisa Nalin, Susanne Andréasson, Anna Wikstrand, Anneli Rydén, Görel Nyman & Marianne Jensen-Waern

  2. Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 751 83, Uppsala, Sweden

    Ram K. Selvaraju, Irina Velikyan, Marie Berglund & Olof Eriksson

  3. Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden

    Irina Velikyan, Marie Berglund & Mark Lubberink

  4. PET Centre, Centre for Medical Imaging, Uppsala University Hospital, Uppsala, Sweden

    Irina Velikyan

  5. Beckman Research Institute of the City of Hope, Duarte, CA, USA

    Fouad Kandeel

  6. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

    Olle Korsgren

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  1. Lovisa Nalin
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Corresponding author

Correspondence to Olof Eriksson.

Additional information

Olof Eriksson, Marianne Jensen-Waern, Lovisa Nalin and Ram K. Selvaraju contributed equally.

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Nalin, L., Selvaraju, R.K., Velikyan, I. et al. Positron emission tomography imaging of the glucagon-like peptide-1 receptor in healthy and streptozotocin-induced diabetic pigs. Eur J Nucl Med Mol Imaging 41, 1800–1810 (2014). https://doi.org/10.1007/s00259-014-2745-3

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  • DOI: https://doi.org/10.1007/s00259-014-2745-3

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