Species differences in pancreatic binding of DO3A-VS-Cys40-Exendin4 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-11

AUTHORS

Olof Eriksson, Ulrika Rosenström, Ram K. Selvaraju, Barbro Eriksson, Irina Velikyan

ABSTRACT

AIMS: Radiolabeled Exendin-4 has been proposed as suitable imaging marker for pancreatic beta cell mass quantification mediated by Glucagon-like peptide-1 receptor (GLP-1R). However, noticeable species variations in basal pancreatic uptake as well as uptake reduction degree due to selective beta cell ablation were observed. METHODS: In vitro and ex vivo autoradiography studies of pancreas were performed using [177Lu]Lu-DO3A-VS-Cys40-Exendin4, in order to investigate the mechanism of uptake as well as the islet uptake contrast in mouse, rat, pig, and non-human primate. The autoradiography results were compared to the in vivo pancreatic uptake as assessed by [68Ga]Ga-DO3A-VS-Cys40-Exendin4 Positron Emission Tomography (PET) in the same species. In vitro, ex vivo, and in vivo data formed the basis for calculating the theoretical in vivo contribution of each pancreatic compartment. RESULTS: [177Lu]Lu-DO3A-VS-Cys40-Exendin4 displayed the highest islet-to-exocrine pancreas ratio (IPR) in rat (IPR 45) followed by non-human primate and mouse at similar levels (IPR approximately 5) while pigs exhibited negligible IPR (1.1). In vivo pancreas uptake was mainly GLP-1R mediated in all species, but the magnitude of uptake under basal physiology varied significantly in decreasing order: non-human primate, mouse, pig, and rat. The theoretical calculation of islet contribution to the total pancreatic PET signal predicted the in vivo observation of differences in pancreatic uptake of [68Ga]Ga-DO3A-VS-Cys40-Exendin4. CONCLUSIONS: IPR as well as the exocrine GLP-1R density is the main determinants of the species variability in pancreatic uptake. Thus, the IPR in human is an important factor for assessing the potential of GLP-1R as an imaging biomarker for pancreatic beta cells. More... »

PAGES

1039-1045

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00592-017-1046-2

DOI

http://dx.doi.org/10.1007/s00592-017-1046-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091514188

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28891030


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