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Dual-modal magnetic resonance/fluorescent zinc probes for pancreatic β-cell mass imaging

Stasiuk, Graeme J.; Minuzzi, Florencia; Sae-Heng, Myra; Rivas, Charlotte; Juretschke, Hans-Paul; Piemonti, Lorenzo; Allegrini, Peter R.; Laurent, Didier; Duckworth, Andrew R.; Beeby, Andrew; Rutter, Guy A.; Long, Nicholas J.

Authors

Graeme J. Stasiuk

Florencia Minuzzi

Myra Sae-Heng

Charlotte Rivas

Hans-Paul Juretschke

Lorenzo Piemonti

Peter R. Allegrini

Didier Laurent

Andrew R. Duckworth

Andrew Beeby

Guy A. Rutter

Nicholas J. Long



Abstract

Despite the contribution of changes in pancreatic β-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 β 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⋅1, binds ZnII directly by means of an amidoquinoline moiety (AQA), thus causing a large ratiometric Stokes shift in the fluorescence from λem=410 to 500 nm with an increase in relaxivity from r1=4.2 up to 4.9 mM−1 s−1. The probe is efficiently accumulated into secretory granules in β-cell-derived lines and isolated islets, but more poorly by non-endocrine cells, and leads to a reduction in T1 in human islets. In vivo murine studies of Gd⋅1 have shown accumulation of the probe in the pancreas with increased signal intensity over 140 minutes.

Publication Date Mar 23, 2015
Journal Chemistry - a European journal
Print ISSN 0947-6539
Electronic ISSN 1521-3765
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 21
Issue 13
Pages 5023-5033
APA6 Citation Stasiuk, G. J., Minuzzi, F., Sae-Heng, M., Rivas, C., Juretschke, H., Piemonti, L., …Long, N. J. (2015). Dual-modal magnetic resonance/fluorescent zinc probes for pancreatic β-cell mass imaging. Chemistry : a European journal, 21(13), 5023-5033. https://doi.org/10.1002/chem.201406008
DOI https://doi.org/10.1002/chem.201406008
Keywords Diabetes; Fluorescence; Imaging agents; Lanthanides; Zinc
Publisher URL http://onlinelibrary.wiley.com/doi/10.1002/chem.201406008/abstract
Copyright Statement © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Additional Information This is a copy of an open access article published in Chemistry - a European journal, 2015, v.21 issue 13.

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Copyright Statement
© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.



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