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 Ca2+ in which the amplification strategy of chemical exchange saturation transfer (CEST) is combined with the broad range of chemical shifts found in F-19 NMR spectroscopy to obtain magnetic resonance images of Ca2+. We exploited the chemical shift change (Delta omega) of F-19 upon binding of Ca2+ 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 Ca2+-bound F-19 frequency and detection of the label transfer to the Ca2+-free F-19 frequency. Through the substrate binding kinetics we were able to amplify the signal of Ca2+ onto free 5F-BAPTA and thus indirectly detect low Ca2+ concentrations with high sensitivity.