Improved FAP-radiotheranostics for personalized cancer treatment
Cancer-associated fibroblasts (CAFs) are a group of tumor stromal cells typically associated with cancer growth and metastasis. These CAFs show high expression of the fibroblast activation protein (FAP) on the cell membrane. Due to the selective FAP expression and cancer-specific distribution, CAFs have emerged as a promising cancer diagnostic marker and an attractive therapeutic target.
The recent success of FAP-targeted positron emission tomography (PET) radiotracers, led to more research for radiopharmaceutical therapies to the protein. Furthermore, a FAP-targeted approach gives the opportunity to use a ligand for both imaging of the expression of FAP and to target it with a radionuclide therapy (theranostics), to enable a personalized cancer treatment. However, the current FAP ligands show suboptimal tumor-residence time, which is of particular importance for radionuclide therapy. Therefore, in this application we aim to develop novel FAP-targeting radiotheranostics. The radiotracers will be first evaluated in vitro to assess FAP selectivity and activity, followed by in vivo imaging and therapy using a human cancer mouse model.