Fluorinated Radiotracers for PET

Our group is focused on cathepsin D (CD), a lysosomal aspartyl protease whose dysregulation can contribute to a number of diseases. Indeed, elevated extracellular levels of CD have been observed in cancers, particularly in triple-negative breast cancer.

CD could therefore serve as a diagnostic biomarker for this condition, and the use of positron emission tomography (PET), a non-invasive imaging technique that detects gamma rays from positron-emitting isotopes, could have a significant impact on the diagnosis and treatment of breast cancer.

To this end, we have developed a "cold" non-radioactive synthesis of new CD ligands that allows the incorporation of a fluorine atom into the peptide scaffold. The first inhibitor synthesized is an analogue of Pepstatin A, which has nanomolar activity on CD. A series of analogues was subsequently synthesized, including one that incorporates trifluoromethionine (TFM) in place of valine.

Next, we will test the biological activity of these new inhibitors on CD, as well as their selectivity against various proteases. The radiochemistry part ("hot" radioactive synthesis) will be carried out in collaboration with the University of Aberdeen (Scotland, UK).