Metal Ion Sensing Using Ion Chemical Exchange Saturation Transfer ~(19)F Magnetic Resonance Imaging

摘要

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 (Δ_ω) of ~(19)F upon binding of Ca~(2+) to the 5,5'-difluoro derivative of l,2-bis(o-aminophenoxy)ethane-Af,N,N~',N~'-tetraacetic acid (5F-BAPTA) by radiofrequency labeling at the Ca~(2+)-bound 19F 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.