title: Near-infrared fluorescent probe for imaging of pancreatic beta cells.
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, and for drug development. Here, using animal models, we report on the synthesis, characterization, and intravital microscopic imaging properties of a near-infrared fluorescent exendin-4 analogue with specificity for the GLP-1 receptor on beta cells (E4(K12)-Fl). The agent demonstrated subnanomolar EC(50) binding concentrations, with high specificity and binding that 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 min and peak fluorescence within 20 min of injection), making this an ideal agent for in vivo imaging.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiner
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Kohler
authors.forename: Chong Wee
authors.initials: CW
authors.lastname: Liew
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Hill
authors.forename: Jason
authors.initials: J
authors.lastname: Gaglia
authors.forename: Rohit N
authors.initials: RN
authors.lastname: Kulkarni
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000077270:Exenatide; D005456:Fluorescent Dyes / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018613:Microscopy, Confocal; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000032:analysis / Q000737:chemistry; D015394:Molecular Structure; D008970:Molecular Weight; D041681:NIH 3T3 Cells; D010455:Peptides / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared; D014407:Tumor Cells, Cultured; D014688:Venoms / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D015335:Molecular Probes; D010455:Peptides; D014688:Venoms; D000077270:Exenatide