A Synthetic Heterobivalent Ligand Composed of Glucagon-Like Peptide 1 and Yohimbine Specifically Targets β Cells Within the Pancreas
Molecular Imaging and Biology, ISSN: 1860-2002, Vol: 17, Issue: 4, Page: 461-470
2015
- 3Citations
- 3Captures
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Metrics Details
- Citations3
- Citation Indexes3
- CrossRef2
- Captures3
- Readers3
Article Description
Purpose: β Cell specificity for a heterobivalent ligand composed of glucagon-like peptide-1 (GLP-1) linked to yohimbine (GLP-1/Yhb) was evaluated to determine its utility as a noninvasive imaging agent. Procedures: Competition binding assays were performed on βTC3 cells and isolated rat islets. Immunostaining for insulin was used to co-localized intravenously injected Cy5-labeled GLP-1/Yhb in β cells of Sprague–Dawley rats. Rats were intravenously injected with In-111-labeled GLP-1/Yhb to determine clearance rates and tissue biodistribution. Tissue-specific binding was confirmed by competition with pre-administration of unlabeled GLP-1/Yhb and in Streptozotocin-induced diabetic rats. Results: In βTC3 cells, high affinity binding of GLP-1/Yhb required interactions with both receptors because monovalent competition or receptor knockdown with RNAi lowered specificity and avidity of the heterobivalent ligand. Binding specificity for isolated islets was 2.6-fold greater than that of acinar tissue or islets pre-incubated with excess unlabeled GLP-1/Yhb. Immunofluorescent localization of Cy5-labeled GLP-1/Yhb was restricted to pancreatic islets. Within 30 min, ~90 % of the In-111-labeled GLP-1/Yhb was cleared from blood. Tissue-specific accumulation of radiolabeled ligand was apparent in the pancreas, but not in other tissues within the abdominal imaging field. Pancreas specificity was lost in Streptozotocin-induced diabetic rats. Conclusions: The GLP-1/Yhb exhibits high specificity for β cells, rapid blood clearance rates, and low non-specific uptake by other tissues within the abdominal imaging field. These characteristics of GLP-1/Yhb are desirable for application to β cell imaging in vivo and provide a basis for developing additional multivalent β cell-specific targeting agents to aid in the management of type 1 diabetes.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84937514754&origin=inward; http://dx.doi.org/10.1007/s11307-014-0817-1; http://www.ncbi.nlm.nih.gov/pubmed/25604385; http://link.springer.com/10.1007/s11307-014-0817-1; https://dx.doi.org/10.1007/s11307-014-0817-1; https://link.springer.com/article/10.1007/s11307-014-0817-1
Springer Science and Business Media LLC
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