Fluorinated probes are attractive for biological studies, using fluorine-19 (¹⁹F) magnetic resonance imaging, because the isotope is almost 100 per cent abundant, and fluoride present naturally in the body does not interfere.  However, the use of ¹⁹F-magnetic resonance is limited by the length of time needed to acquire a spectrum.  Now researchers at Durham University, UK have found a possible solution to this problem.

Nuclear magnetic resonance (NMR) spectroscopy relies on the absorption of radiofrequency radiation to move nuclei between the energy levels created when they are placed in magnetic field.  To achieve a good signal to noise ratio, it is necessary to provide several pulses of radiation.  Between each pulse, the system must be allowed to relax or re-equilibrate, and it's fluorine's very long relaxation time that is the route cause of the problem.

David Parker and colleagues have shown that the incorporation of a fluorinated reporter group close to the metal in a lanthanide complex can overcome this problem.  The lanthanide 'catalyses' the relaxation process, meaning that spectra can be obtained in just ten minutes.

'An added benefit is that the lanthanide also enhances the difference in chemical shift between similar environments meaning that even small changes can be measured,' said Parker, 'and by setting the relaxation times for our experiment carefully we can even use this property as a time-gate that eliminates all but the signals we are interested in.'

'Developing such ¹⁹F-NMR-lanthanide probes looks very attractive,' said David O'Hagan, an expert in biotransformations from the University of St Andrews, UK.  'One might imagine a lanthanide CF₃-ligand complex with an oligonucleotide probe, or a small molecule attached, designed to hybridise to a particular gene, protein or receptor, or alternatively linked to a small molecule substrate which gets chemically changed when the gene for an enzyme is up-regulated in cells.' 

Parker said that the next step will be to apply this technique for in vitro enzyme monitoring, and because similar complexes have already been used in vivo, real time experiments studying, for example, the effect of drugs on the expression of certain genes may not be too far away.

Ralph Mason, an expert in Radiology from the University of Texas, Southwestern Medical Centre, said 'These molecules could add to the armoury of reporter molecules used in molecular imaging.  It may be possible for example, to measure changes in pH which is difficult to achieve using standard 1H techniques because the signals from water cause problems.  It is potentially very exciting.'

Stephen Davey