To summarize the biological basis of FAP targeting, radiopharmaceutical design, clinical imaging applications, benign fibro-inflammatory pitfalls, and early therapeutic development related to FAP inhibitors.
Approach:
Biological rationale: FAP-targeted imaging focuses on activated stromal biology, which can be useful when tumor-cell metabolism is low or obscured by physiologic tracer activity.
Radiopharmaceutical design: The review discusses the design of FAPI tracers, including the combination of FAP-binding inhibitors with linkers and chelators, and their impact on pharmacokinetics.
Key Findings:
FAPI PET provides high lesion-to-background contrast in desmoplastic and low-FDG-avid tumors.
FAPI uptake is not tumor-specific and can occur in benign fibro-inflammatory conditions such as wound healing, fibrosis, and pancreatitis.
Current clinical applications include gastrointestinal cancers, peritoneal disease, and hepatocellular carcinoma.
First-generation monomeric tracers may wash out rapidly and have heterogeneous FAP expression.
Interpretation:
FAPI PET is a complementary imaging method for FAP-targeted radionuclide therapy and should not be considered a universal replacement for established imaging.
Limitations:
Prospective dosimetry and outcome data for FAP-targeted therapy remain limited.
Benign uptake must be carefully correlated with other imaging modalities and clinical history.
Conclusion:
Future research should focus on standardized acquisition, disease-specific indications, and prospective trials to assess management impact and patient outcomes.
