Design and Synthesis of MRI-Based Molecular Biosensors for Monitoring Zn²⁺

Zinc (Zn²⁺) is the second most abundant metal ion in the human body and it plays a pivotal role in various cellular process in health and disease.¹ Therefore it is very important to develop methodologies for longitudinal visualization and quantification of labile Zn²⁺ levels from live intact subjects. The light signal source of fluorescence Zn²⁺-sensors don’t allow their use in deep tissues of live subject and therefore molecular probes for MRI applications should be considered. Several MRI-sensors for monitoring labile Zn²⁺ have been suggested based on T₁-contrast enhancement with Gd based contrast agent²,¹²⁹Xe-NMR³,¹⁹F-CEST MRI⁴.

¹⁹F-based sensors for MRI applications show several advantages over the MRI metal based contrast agents, due to negligible amount of ¹⁹F in biological tissue and no background,100% natural isotope abundance of ¹⁹F. Here we show that ¹⁹F-modified dipicolylamine derivatives have the potential to be used as ¹⁹F-CEST sensors for Zn²⁺ monitoring with MRI. The synthesis of the library of the ¹⁹F-probes and their binding properties towards Zn²⁺ ions is discussed. One compound showed the potentiality to be used as MRI-based probe for spatially monitoring Zn²⁺ with MRI. The ability to amplify the ¹⁹F-signal through saturation transfer and thus monitoring low concentrations of Zn²⁺ should allow us to proceed to biological models.

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