Fibroblast activation protein (FAP) is overexpressed in the tumor microenvironment or stroma of over 90% of solid tumors, what makes it a promising target for both therapeutic and molecular imaging applications. FAP-targeting molecular imaging has been quickly gaining steam in cancer diagnostics. It is especially useful for tumors with a strong desmoplastic (forming fibrous tissue) reaction, such as breast, colon, and pancreatic cancers.
This diagnostic method is characterized by high detection rate in a variety of tumors, even in cases considered to be challenging for the conventional 18F-FDG PET. Tumor stroma is reported to develop around malignant cells exceeding a size of 1–2 mm, and FAP is hardly expressed in quiescent fibroblasts or in healthy adult tissues. So FAPI scan helps detect microscopic primary or metastatic lesions in crucial organs like the brain, liver, pancreas, and gastrointestinal tract and shows high lesion uptake with sharp image contrast.
FAPI PET is independent of glucose activity, leading to the drastic reduction of nonspecific and physiologic radiotracer uptake in the glucose-rich tissues, like brain, liver or gastrointestinal tract. It is ideal for selective imaging of pathologic changes with low background signal. In practical use, FAPI PET can be used without any dietary preparation and provides stable tracer uptake 10 minutes to 3 hours after administration.
Tumor stroma appears not only to provide mechanical and nutritional support to the malignant cells but also to be fundamentally involved in tumor progression, invasion, metastasis, immunosurveillance, and drug resistance. Destroying the stroma may not only cut off “supply lines” to cancer cells, but also improve the effects of conventional therapies and expose the cancer cells to the own immune forces of the body (video credit @SlaatsJeroen Twitter). Therefore, the fact that FAP is not present in the healthy tissues makes cancer-associated fibroblasts an attractive target for antitumor therapy. The success of the FAPi-based radioligand therapy is contingent on the time the radionuclide remains in the body to enable it to have an effect. So far it has been a struggle. All ligands developed thus far get washed out of the tumor tissue relatively rapidly, what limits the delivery of the radiation dose of the common therapeutic emitters, like lutetium or actinium. Scientists have been tirelessly working on developing new forms of ligands.
Scientific articles of interest:
- FAPI PET: Fibroblast Activation Protein Inhibitor Use in Oncologic and Nononcologic Disease
- FAPI-PET/CT in Cancer Imaging: A Potential Novel Molecule of the Century
- Influence of Cirrhosis on 68Ga-FAPI PET/CT in Intrahepatic Tumors
- Fibroblast Activation Protein Inhibitor–Based Radionuclide Therapies: Current Status and Future Directions
- Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions
- Evaluation of the Diagnostic Accuracy of FAPI PET/CT in Oncologic Studies: Systematic Review and Metaanalysis
- Next generation radiotheranostics promoting precision medicine
- The Latest Developments in Imaging of Fibroblast Activation Protein
- 68Ga-FAPI-PET/CT in patients with various gynecological malignancies
- 68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer
- State-of-the-art of FAPI-PET imaging: a systematic review and meta-analysis
- Initial clinical experience with 90Y-FAPI-46 radioligand therapy for advanced-stage solid tumors: a case series of 9 patients
- Increased 68Ga-FAPI Uptake in Active Atherosclerotic Plaque
- First Patient Imaged in SOFIE’s 18F-FAPI Phase 2 trial (Pancreatic Ductal Adenocarcinoma)
- Fibroblast-Activation Protein PET and Histopathology in a Single-Center Database of 324 Patients and 21 Tumor Entities
- Novel PET radiotracer shows promise in cancer imaging
- New research: FAPI PET imaging superior for diagnosing multiple types of cancer, with potential for targeted treatment