科研之友
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摘要
Despite the contribution of changes in pancreatic beta-cell mass to the development of all forms of diabetes mellitus, few robust approaches currently exist to monitor these changes prospectively in vivo. Although magnetic-resonance imaging (MRI) provides a potentially useful technique, targeting MRI-active probes to the beta cell has proved challenging. Zinc ions are highly concentrated in the secretory granule, but they are relatively less abundant in the exocrine pancreas and in other tissues. We have therefore developed functional dual-modal probes based on transition-metal chelates capable of binding zinc. The first of these, Gd center dot 1, binds Zn-II directly by means of an amidoquinoline moiety (AQA), thus causing a large ratiometric Stokes shift in the fluorescence from lambda(em)= 410 to 500 nm with an increase in relaxivity from r(1)= 4.2 up to 4.9 mm(-1) s(-1). The probe is efficiently accumulated into secretory granules in beta-cell-derived lines and isolated islets, but more poorly by non-endocrine cells, and leads to a reduction in T-1 in human islets. In vivo murine studies of Gd center dot 1 have shown accumulation of the probe in the pancreas with increased signal intensity over 140 minutes.
- 出版日期2015-3-23
