Improved PET capabilities

The PET tracer is prepared by tagging a molecule normally used by the body with a radioactive atom. PET often employs glucose, the body's fuel. Glucose metabolism (building up and breaking down) in terms of rate and location provides important information about biochemical changes associated with the onset or progression of a disease.

Glucose is most often tagged with radioactive fluorine to create a radionuclide called fluorodeoxyglucose (FDG). FDG is injected intravenously. As it decays, it emits positrons and eventually creates gamma rays that can be detected by a scanner.

Currently, PET is limited by the short half-life of fluorine-18 (18F) and its small number of compatible functional groups. This means it must be introduced close to injection time and can only tag a small number of simple molecules. Scientists sought to expand the capabilities of PET with EU funding of the project 'Late stage fluorination for positron emission tomography applications' (FLUOPET).

Building on recent advances by partner scientists in late-stage fluorination with 19F, investigators sought first to improve those methods. They demonstrated excellent success using a common commercial reagent (PhenofluorTM) at room temperature, meaning compatibility with temperature-sensitive substrates. In addition, the synthesis process substantially reduced or even eliminated typical side reactions and demonstrated broad functional group compatibility with synthetically useful selectivity.

In the second year, the team focused on adaptation of the methods from 19F to 18F. Numerous PhenofluorTM-type reagents were successfully prepared. However, their selective fluorination with 18F has proved more complicated. Experiments are ongoing to improve it.

During the development of analogues of PhenofluorTM, scientists serendipitously created a solid complex containing an important reagent for trifluoromethylation (trifluoroiodomethane, or CF3I). It is typically in gaseous form in which its usefulness was more limited. Researchers demonstrated its practicality and sometimes greater reactivity compared to the gaseous form. A patent application has been filed and a publication submitted.

FLUOPET launched the development of improved PET tracers for imaging the metabolism of complex molecules such as neurotransmitter receptors. Continued work is expected to greatly advance the capabilities of an already powerful non-invasive technique to diagnose and follow the progression of numerous diseases.