Metal ion sensing using ion chemical exchange saturation transfer 19F magnetic resonance imaging

Although metal ions are involved in a myriad of biological processes, noninvasive detection of free metal ions in deep tissue remains a formidable challenge. We present an approach for specific sensing of the presence of Ca(2+) in which the amplification strategy of chemical exchange saturation transfer (CEST) is combined with the broad range of chemical shifts found in (19)F NMR spectroscopy to obtain magnetic resonance images of Ca(2+). We exploited the chemical shift change (Δω) of (19)F upon binding of Ca(2+) to the 5,5'-difluoro derivative of 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F-BAPTA) by radiofrequency labeling at the Ca(2+)-bound (19)F frequency and detection of the label transfer to the Ca(2+)-free (19)F frequency. Through the substrate binding kinetics we were able to amplify the signal of Ca(2+) onto free 5F-BAPTA and thus indirectly detect low Ca(2+) concentrations with high sensitivity.