Magnetic resonance imaging (MRI) is widely utilized in medical imaging because it is noninvasive and does not use potentially hazardous x-rays. MRI uses radio waves to create contrast between different tissues in the body.
Isotopes of elements are utilized in MRI for imaging purposes. An isotope of an element possesses the usual number of protons, but a different number of neutrons.
An isotope of hydrogen, denoted as hydrogen-1, is the most widely utilized isotope in MRI. This is because hydrogen atoms are present throughout the body.
A potentially analogously useful isotope for MRI is fluorine-19. Since fluorine atoms are not common in the body, its use is as an imaging tracer for collecting information about drugs (what form, how much, and where) in the body.
The use of fluorine atoms in MRI requires that some of the drug be mixed in somehow with fluorine atoms. However, common methods of doing so result in the accumulation of fluorine in the body for months, require complex drug processing, generate imaging artifacts and low imaging contrast, and are not stable in the body.
Yihua Yu (University of Maryland) and coworkers have overcome these limitations. They have developed an improved fluorine imaging tracer for magnetic resonance imaging.
The imaging tracer.
The scientists' imaging tracer possesses 27 fluorine atoms, arranged symmetrically in the molecule. This means that they all contribute to one MRI signal, enhancing image intensity and reducing the time required for data collection.
The tracer also possesses symmetrically-arranged water-soluble units at the other end of the molecule. This means that the water-soluble units will not break the symmetry of the fluorine atoms.
Imaging in mice.
The scientists injected a small amount of the imaging tracer in mice, and observed their internal organs with MRI. The imaging tracer became invisible after at most two hours, except in the bladder.
This means that the imaging agent is rapidly excreted, which is ideal for MRI. The scientists estimate a half-life (the time required for half of the tracer to be excreted) of 12 hours in the body, far shorter than the months observed with other fluorine imaging tracers.
The imaging tracer is stable in the body, as evidenced by unchanged spectra in MRI and chromatography experiments. Additionally, no obvious toxicity was evident in the mice, suggesting that the imaging tracer is safe.
Future challenges.
While the scientists' imaging tracer is vastly improved over other fluorine formulations, there are still challenges to be overcome. One is that only a relatively small number of fluorine atoms can be used in the tracer, which limits its sensitivity.
Another challenge is that the tracer, as envisioned in this formulation, is not chemically bound to a drug molecule. Therefore, it is unclear if it will remain in proximity to the drug over the course of imaging.
Alternatively, chemically affixing the tracer to a drug molecule, to ensure proximity, will alter the bioactivity of the drug. The scientists envision solving this dillema by mixing the imaging tracer with a "prodrug," a molecule that is only converted into the intended drug molecule when it reaches its destination, such as a tumor.
They are currently pursuing these research directions. The advantages of simple processing, unambiguous imaging data, stability, nontoxicity, and short residence time in the body suggest that this fluorine imaging agent will greatly assist the medical community to rapidly and noninvasively gather information on drugs in the body with magnetic resonance imaging.
for more information:
Jiang, Z.-X., Liu, X., Jeong, E.-K., & Yu, Y. B. (2009). Symmetry-Guided Design and Fluorous Synthesis of a Stable and Rapidly Excreted Imaging Tracer for
19F MRI
Angewandte Chemie International Edition, 48 (26), 4755-4758 DOI: 10.1002/anie.200901005