Intrusive biopsies for people with cancer could be sidestepped thanks to the development of fluorine-containing contrast agents by David Parker and colleagues at Durham University.

The lack of fluorine chemistry in the human body would allow an MRI scan following injection of a fluorine-containing contrast agent. This could, for example provide a detailed view of acidic regions, such as those containing cancer cells. The new class of agents essentially adds chemical sensitivity to MRI and could be used to track disease progression without the need to take tissue or fluid samples.

"There is very little fluorine present naturally in the body so the signal from our compound stands out," Parker explains. The team, which includes Kanthi Senanayake, Alan Kenwright, and Susanna van der Hoorn, has added CF₃ reporter groups close to the paramagnetic centre in macrocyclic lanthanide(III) complexes. "By carefully considering the probe design, the fluorine shift can be tuned to resonate at differing frequencies, e.g. depending on the acidity or enzyme levels in a certain area, offering the potential to locate and highlight cancerous tissue."

These agents allow faster acquisition of ¹⁹F magnetic resonance data, say the researchers, as well as amplifying chemical shift non-equivalence. This will allow detailed magnetic resonance information to be obtained quickly and at a dosage below the safety threshold. "We have taken an important first step towards the development of a selective new imaging method," explains Parker, "However, we appreciate that there is a lot of work to do to take this laboratory work and put it into practice. In principle, this approach could be of considerable benefit in the diagnosis of diseases such as breast, liver or prostate cancer." Durham University has filed for patent protection on this new approach and is now looking for commercial partners. Parker suggests that fluorine contrast agents could enter mainstream MRI use within ten years. "This development could have applications in many other disease states too."

"A key point is that ¹⁹F MR spectroscopy and imaging can be undertaken on the same instruments used for (proton) MRI," Parker told SpectroscopyNOW. At present, Phillips and other instrument manufacturers are making progress in developing the instruments (hardware/software) for ¹⁹F NMR applications typically using conventional perfluorocarbons as contrast media. "We have critically enhanced the relaxation rate of the ¹⁹F nucleus in the complex by a factor of 100 so the signal intensity gain is at least an order of magnitude, enhancing sensitivity," adds Parker.

Once transferred from the lab to the hospital bedside, this research has the potential to help show exactly where cancer may be in the body. This would add certainty to treatment decisions and improve monitoring of cancer progress.
Parker adds that he and his colleagues are working as part of an EPSRC team funded from 2006 to 2010 to develop "Functional Ligands for Imaging in Cancer". The collaboration is organised with Newcastle University researchers, Andrew Blamire and Ross Maxwell and includes NE-CRC colleagues Roger Griffin and Herbie Hewell. "Our remit is to develop better imaging protocols related to cancer diagnosis," Parker told us. At present the research is awash in bodily fluids but the imminent arrival of an animal scanner will likely accelerate development of the technology.

Related links:

• Chem Commun, 2007, 2923-2925  
• Professor David Parker Page

Article by David Bradley