Aryl-Phosphonate Lanthanide Complexes and Their Fluorinated Derivatives: Investigation of Their Unusual Relaxometric Behavior and Potential Application as Dual Frequency1H/19F MRI Probes

A series of low molecular weight lanthanide complexes were developed that have high (1)H longitudinal relaxivities (r1) and the potential to be used as dual frequency (1)H and (19)F MR probes. Their behavior was investigated in more detail through relaxometry, pH-potentiometry, luminescence, and multinuclear NMR spectroscopy. Fitting of the (1)H NMRD and (17)O NMR profiles demonstrated a very short water residence lifetime (10 ns) and an appreciable second sphere effect. At lower field strengths (20 MHz), two of the complexes displayed a peak in r1 (21.7 and 16.3 mM(-1) s(-1)) caused by an agglomeration, that can be disrupted through the addition of phosphate anions. NMR spectroscopy revealed that at least two species are present in solution interconverting through an intramolecular binding process. Two complexes provided a suitable signal in (19)F NMR spectroscopy and through the selection of optimized imaging parameters, phantom images were obtained in a MRI scanner at concentrations as low as 1 mM. The developed probes could be visualized through both (1)H and (19)F MRI, showing their capability to function as dual frequency MRI contrast agents.