Associated with the development of all types of diabetes is the depletion of pancreatic β-cell mass. It is known that Zn2+ is co-released with insulin from the β-cells in response to high glucose levels. Thus, by determination of Zn2+ concentrations in the insulin granules, β-cell mass can be quantified to understand how its deterioration, and progression affects the onset and progression of diabetes. There are however, few probes capable of this function. By the combination of two or more imaging techniques, the limitations associated with each technique can be synergistically overcome. This work describes developments towards a dual-modal magnetic resonance (MR)/near-infrared (NIR) imaging agent that selectively binds to Zn2+ ions within the pancreas, to ultimately achieve a more profound understanding of the role that zinc plays in diabetes. A novel gadolinium containing dual-modal NIR/MR fluorescent cyanine based contrast agent (GdCy-BP) has been synthesized bearing a BPEN moiety in order to chelate to free Zn2+ in the body. Preliminary studies have shown the probe to have an excitation wavelength of 620 nm and an emission wavelength of 750 nm, exhibiting an emission well into the NIR region, promoting optimum tissue penetration and reduced background interference. Titration experiments have demonstrated the selectivity of GdCy-BP for Zn2+ ions over other small ions, and the ability to detect changes in the concentration of Zn2+ through changes in the fluorescence intensity upon increasing equivalents of Zn2+ ions. In vitro analysis of the NIR contrast agent is currently on-going, alongside a complete in vivo MRI analysis, to demonstrate the utility of this probe for the detection of pancreatic Zn2+ ions associated with the disease diabetes.

Dual-modal MR/NIR fluorescent probes for zinc sensing applications

253rd National Meeting (2017)

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