Pancreatic beta-cells are responsible for the production and release of insulin, a hormone that controls the level of glucose in the blood. Beta-cell mass is markedly reduced in both insulin-dependent and non-insulin-dependent diabetes mellitus. [1][2][3][4][5] The noninvasive estimation of beta-cell mass by imaging would have a significant impact on the management of clinical diabetes, pancreas-and/or isletcell transplantation, and the understanding of the pathogenesis of the disease. Currently, measurements of insulin secretion and c-peptide production serve as surrogates for the assessment of beta-cell function. [6] However, these methods are not suitable for in vivo detection. Previously several attempts have been made by us and other investigators to image pancreatic-islet inflammation, rejection, and transplantation. [7][8][9][10][11][12][13] Here, we describe the synthesis and testing of near-infrared (NIR) probes for imaging beta-cells in pancreatic islets, based on the beta-cellspecific ligand streptozotocin (STZ), labeled with the fluorescent dye cyanine-5.5 (Cy5.5).
Our probe design is based on the specificity of STZ for beta-cells and the following well-known facts. STZ is an FDAapproved drug for treating metastatic cancer of pancreaticislet cells. [14] However, in the diabetes-research community, STZ is also widely used to establish mouse models of Type 1 diabetes, and this capability is ascribed to its specific toxicity to murine beta-cells. [15,16] It is believed that the selective targeting of STZ toward beta-cells is rooted in a specific