Researchers have found a versatile workaround to create chemical compounds that could prove useful for medical imaging and drug development. While studying chemical reactions of a gold-containing molecule, a research team happened upon a chemical mechanism that can be used to form trifluoromethyl (CF3) compounds and attach them to other chemical compounds. This discovery could aid in the synthesis of new “radiotracers” – chemical compounds that contain a radioactive isotope of an element – for use with PET (positron emission tomography) scanning.
Drug companies have shown an increasing interest in incorporating CF3 compounds – which contain carbon and fluorine – in a range of pharmaceuticals. In testing the biological uptake of drugs that incorporate these compounds, it's useful to incorporate fluorine-18 (18F), a radioactive isotope of fluorine, in the CF3 compound as a sort of label or “tracer” that can be detected by PET scanners.
Although CF3 groups have long been known as medicinal chemistry boons, they were traditionally very difficult to install. However a chemical technique, based on a new discovery in gold chemistry, enables attachment of a radioactive fluorine atom to a specific class of molecule that was previously challenging to do.
PET scans are commonly used to detect, map, and monitor internal cancers. They also can produce detailed images of the brain and other organs and help drug developers trace the biological pathways, concentration, and dispersal of new drugs.
The research team tapped the mechanism to incorporate fluorine-18 in CF3 compounds they created. Fluorine-18 is a popular tracer for revealing cancers and other biological targets in PET scans.
Flourine-18 has a half-life of about 110 minutes, which means its radioactive output is halved every 110 minutes, and the chemical processes incorporating it as a label must be designed to rapidly attach it to compounds of interest. In other work, a team of researchers had been pursuing a chemical process to produce a fluorine-containing compound called hexafluoroethane, used to etch silicon for computer chips, associated with a gold-containing molecule. In this effort, they enlisted a boron-containing compound. Unexpectedly, they found a mechanism by which the boron compound acts on a CF3 compound to produce a CF3 fragment associated with the gold catalyst. This fragment, they observed, can then bond with other chemical compounds and in a next step form a new CF3-containing compound. They manipulated this mechanism to derive drug compounds including leflunomide, a drug that is used to reduce swelling and inflammation in the treatment of rheumatoid arthritis, for example, and also a painkiller known as BAY 59-3074.
The pharmaceutical field and the diagnostic medicine field have been very limited in getting compounds that have been labeled with radioactive CF3 and yet there are a lot of drugs that have these CF3 groups in them. The research team learned how to incorporate the fluorine-18 marker atoms into the chemical mechanism they used to create new compounds. The researchers think these gold compounds will be a powerful platform to prepare new tracers, and are working to improve the system and to identify promising, clinically-relevant drug targets. Also, the new mechanism could shed light on broader problems in chemistry by providing a deeper understanding of fundamental reaction processes for gold and other catalysts.
For more information, contact Jon Weiner at 510-486-4014.