A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Tumor stroma, rich in cancer-associated fibroblasts (CAFs), is a key component of epithelial carcinomas.
• Cancer-associated fibroblasts overexpress fibroblast activation protein (FAP), a marker associated with poor prognosis.
• FAP is largely absent in healthy adult tissues, making it a promising target for cancer diagnostics and therapeutics.

Purpose of the Study:

• To develop and evaluate novel radiotracers targeting fibroblast activation protein (FAP) for improved cancer imaging.
• To assess the in vitro and in vivo performance of FAP-specific enzyme inhibitors (FAPI) as diagnostic agents.
• To demonstrate the clinical utility of FAPI-based imaging in cancer patients.

Main Methods:

• Development of iodinated and DOTA-coupled FAP-specific enzyme inhibitors (FAPI).
• In vitro evaluation including uptake, competition, and efflux studies.
• In vivo imaging and biodistribution studies in tumor-bearing animals and human patients using 68Ga-labeled FAPI.

Main Results:

• FAPI demonstrated high specificity, affinity, and rapid internalization into FAP-expressing cells.
• High intratumoral uptake and fast body clearance were observed in preclinical models and human patients.
• FAPI imaging provided high-contrast images with minimal radiation exposure to healthy tissues.
• FAPI outperformed 18F-FDG in a comparative lung adenocarcinoma imaging study.

Conclusions:

• Radiolabeled FAPIs enable rapid, high-contrast imaging of tumors with high stromal content, acting as potential pantumor agents.
• The DOTA-coupling allows for versatile labeling with various isotopes, including diagnostic (68Ga) and therapeutic (177Lu, 90Y) radionuclides.
• FAPI represents a promising platform for both diagnostic imaging and targeted radionuclide therapy in oncology.