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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 9/2014

01.09.2014 | Original Article

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

verfasst von: Lovisa Nalin, Ram K. Selvaraju, Irina Velikyan, Marie Berglund, Susanne Andréasson, Anna Wikstrand, Anneli Rydén, Mark Lubberink, Fouad Kandeel, Görel Nyman, Olle Korsgren, Olof Eriksson, Marianne Jensen-Waern

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 9/2014

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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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Metadaten
Titel
Positron emission tomography imaging of the glucagon-like peptide-1 receptor in healthy and streptozotocin-induced diabetic pigs
verfasst von
Lovisa Nalin
Ram K. Selvaraju
Irina Velikyan
Marie Berglund
Susanne Andréasson
Anna Wikstrand
Anneli Rydén
Mark Lubberink
Fouad Kandeel
Görel Nyman
Olle Korsgren
Olof Eriksson
Marianne Jensen-Waern
Publikationsdatum
01.09.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 9/2014
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-014-2745-3

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