Synthesis and testing of beta-cell specific Streptozotocin-derivated near infrared imaging probes

BIOL 98

Chongzhao Ran, cran@nmr.mgh.harvard.edu, Pamela Pantazopoulos, PPANTAZOPOULOS@PARTNERS.ORG, Zdravka Medarova, and Anna Moore. Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, 13th Street, Charlestown, MA 02129
Pancreatic beta-cell mass is markedly reduced in both insulin-dependent and non-insulin-dependent diabetes mellitus. The non-invasive estimation of beta-cells mass by imaging would have significant impact in managing clinical diabetes, pancreas and/or islet cell transplantation and the understanding of the pathogenesis of the disease. In order to synthesize an imaging probe specific for pancreatic beta-cells, we derivatized streptozotocin (STZ), which has a known specificity to the GLUT2 receptor on beta-cells. Starting from from glucosamine, two probes were synthesized through multiple steps and conjugation with Cy5.5 dye, which enables near-infrared optical imaging. The specificities of the two designated probes were confirmed in cell-based assays using INS-1E cells as well as by confocal microscopy with human pancreatic islets. The GLUT-2 inhibitor phloterin showed significant inhibition of the binding by both probes. The studies on probe specificity were corroborated by FACS analysis. TUNEL analysis showed no elevated toxicity of the probes compared to untreated human islets or islets treated with parental STZ.
 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007