The Latest Developments in Imaging of Fibroblast Activation Protein

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts, correlating with tumor progression and poor prognosis.
• FAP is a promising target for radionuclide-based cancer diagnosis and treatment, as well as for nonmalignant extracellular matrix remodeling diseases.

Purpose of the Study:

• To develop and evaluate quinolone-based FAP inhibitors (FAPIs) for targeted radionuclide imaging.
• To assess the diagnostic performance of FAPI PET/CT compared to standard imaging techniques.

Main Methods:

• Development of quinolone-based FAPIs conjugated to chelators for radionuclide labeling.
• Evaluation of FAPI binding affinity, internalization, and specificity in human and murine FAP models.
• Assessment of in vivo tumor uptake, biodistribution, and pharmacokinetic properties in preclinical models.
• Comparison of FAPI PET/CT imaging with 18F-FDG PET/CT in various tumor types.

Main Results:

• Developed FAPIs demonstrated specific binding and rapid internalization into FAP-expressing cells.
• High tumor uptake and rapid clearance from normal tissues resulted in excellent image contrast for FAPI PET/CT.
• FAPI PET/CT achieved high diagnostic quality imaging as early as 10 minutes post-injection.
• FAPI PET/CT showed advantages over 18F-FDG PET/CT in staging, recurrence detection, and metastasis identification, including peritonitis carcinomatosa.

Conclusions:

• Quinolone-based FAPIs are effective targeted agents for radionuclide imaging of FAP-expressing tumors.
• FAPI PET/CT offers a highly sensitive and specific imaging modality with rapid acquisition times.
• FAPI PET/CT presents a valuable alternative and complementary tool to 18F-FDG PET/CT for oncological imaging and diagnosis.