Imaging β-Cell Death With a Near-Infrared Probe

  1. Zdravka Medarova1,
  2. Susan Bonner-Weir2,
  3. Myra Lipes2 and
  4. Anna Moore1
  1. 1MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts
  2. 2Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
  1. Address correspondence and reprint requests to Anna Moore, PhD, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Room 2301, Building 149, 13th St., Charlestown, MA 02129. E-mail: amoore{at}helix.mgh.harvard.edu

Abstract

Evidence exists for an essential role of β-cell apoptosis in the pathology of type 1 and type 2 diabetes. Current methods for diabetes-associated apoptosis detection, however, suffer the drawbacks of relying on in situ–based strategies. In this study, we attempted to measure, both in vitro and ex vivo, levels of β-cell apoptosis in diabetic mice using Cy5.5-labeled annexin V. We used streptozotocin-treated BALB/c mice and NOD mice of different ages as models of type 1 diabetes and db/db mice as a model of type 2 diabetes. With annexin V Cy5.5, we established differences in levels of apoptosis between diabetic and control animals. Intravenously administered annexin V Cy5.5 accumulated in pancreata of diabetic mice but not in nondiabetic controls. Furthermore, its localization was specific to apoptotic events within diabetic islets; its selectivity was supported by transferase-mediated dUTP nick-end labeling staining. Because annexin V defines an early marker of apoptosis and the developed probe is suitable for in vivo administration, it may provide a promising tool for real-time identification in intact animals of the earliest stages of diabetes-associated β-cell death and for tracing the events that characterize the pathology of the disease.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted February 22, 2005.
    • Received September 13, 2004.
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