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      1. Author :
        Thomas Reiner, Rainer H. Kohler, Chong Wee Liew, Jonathan Hill, Jason Gaglia, Rohit Kulkarni and Ralph Weissleder
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Bioconjugate Chemistry
      6. Products :
      7. Volume :
        21
      8. Issue :
        7
      9. Page Numbers :
        N/A
      10. Research Area :
        Metabolic Disorders
      11. Keywords :
        Beta-cells; GLP1-R; imaging; targeting; in vivo imaging; VivoTag; AngioSense; Diabetes
      12. Abstract :
        The ability to image and ultimately quantitate beta-cell mass in vivo will likely have far reaching implications in the study of diabetes biology, in the monitoring of disease progression or response to treatment, as well as for drug development. Here, using animal models, we report on the synthesis, characterization of, and intravital microscopic imaging properties of a near infrared fluorescent exendin-4 analogue with specificity for the GLP-1 receptor on beta cells (E4K12-Fl). The agent demonstrated sub-nanomolar EC50 binding concentrations, with high specificity and binding could be inhibited by GLP-1R agonists. Following intravenous administration to mice, pancreatic islets were readily distinguishable from exocrine pancreas, achieving target-to-background ratios within the pancreas of 6:1, as measured by intravital microscopy. Serial imaging revealed rapid accumulation kinetics (with initial signal within the islets detectable within 3 minutes and peak fluorescence within 20 minutes of injection) making this an ideal agent for in vivo imaging.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912453/?tool=pubmed
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4561
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