Research Maarten Vanermen

Abstract

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 this protein. Furthermore, a FAP-targeted approach gives the opportunity to use a using the same ligand for both imaging of the expression of FAP and to target it with a radionuclide therapy (theranostics), to enables a personalized cancer treatmentmedicine approach. 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.

Researcher(s)

• Promoter: Elvas Filipe
• Co-promoter: Van den Wyngaert Tim
• Co-promoter: Van Der Veken Pieter
• Fellow: Vanermen Maarten

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project

Abstract

Fibroblast activation protein (FAP) is a serine protease expressed on stromal cells of > 90% of all epithelial cancers, whereas its expression is almost undetected in normal tissues. In addition, FAP expression is highly restricted and transiently increased in adult tissues during wound healing, inflammation or fibrosis in activated fibroblasts. Among the stromal cells, cancer associated fibroblasts (CAFs) having a FAP-positive phenotype have been associated with poor prognosis in multiple cancers. The highly focal expression and cancer-specific distribution of FAP make this protein a promising cancer diagnostic marker and an attractive therapeutic target. Motivated by the success of FAP-targeted positron emission tomography (PET) radiotracers, FAP-targeted radiopharmaceutical therapies are currently heavily investigated. In addition, FAP-targeted radiopharmaceuticals offer the possibility of imaging diagnostics and targeted radionuclide therapy using the same ligand (theranostics), enabling personalized cancer treatment. However, the relatively rapid washout from the tumor and inadequate pharmacokinetics of current FAP ligands represents a major problem for radioligand therapy. Therefore, the goal of this application is to develop FAP-targeting radiotheranostics. Radiotracers will be evaluated in vitro to assess FAP activity and selectivity. Finally, a human cancer mouse model will be used to assess both imaging and therapeutic potential of our FAP- radiotracers. If successful, our strategy will help physicians select patients who can benefit from FAP-targeted radionuclide therapy.

Researcher(s)

• Promoter: Elvas Filipe
• Co-promoter: Van den Wyngaert Tim
• Co-promoter: Van Der Veken Pieter
• Fellow: Vanermen Maarten

Research team(s)

• Molecular Imaging and Radiology (MIRA)

Project type(s)

• Research Project