FAPI diagnostics

June 27, 2023April 9, 2024anastasiaNews

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 boasts an exceptional detection rate across a spectrum of tumors, even in scenarios traditionally deemed challenging for conventional ¹⁸F-FDG PET. The emergence of tumor stroma surrounding malignant cells, typically exceeding a size threshold of 1–2 mm, coupled with minimal expression of FAP in quiescent fibroblasts or healthy adult tissues, underscores the efficacy of FAPI scanning. This cutting-edge technique facilitates the detection of microscopic primary or metastatic lesions in vital organs such as the brain, liver, pancreas, and gastrointestinal tract, revealing pronounced lesion uptake alongside striking image contrast.

FAPI PET works independently of glucose activity, resulting in a marked reduction of nonspecific and physiologic radiotracer uptake in glucose-rich tissues like the brain, liver, or gastrointestinal tract. This characteristic makes it ideally suited for targeted imaging of pathological changes against a backdrop of minimal background signal. Furthermore, the practicality of FAPI PET shines through its seamless integration into clinical workflow – no dietary preparation required, and offering consistent tracer uptake between 10 minutes to 3 hours post-administration.

The tumor stroma serves not only as a mechanical and nutritional scaffold for malignant cells but also plays a crucial role in tumor advancement, invasion, metastasis, immune surveillance, and drug resistance. Destroying the stroma not only severs the "supply lines" to cancer cells but also enhances the efficacy of standard therapies, unveiling cancer cells to the body's innate immune defenses. (video credit @SlaatsJeroen Twitter). Hence, the absence of FAP in healthy tissues renders cancer-associated fibroblasts an appealing target for antitumor therapy. However, the effectiveness of FAPi-based radioligand therapy hinges on the duration of radionuclide retention within the body to exert its therapeutic effects. Thus far, this has proven challenging. Existing ligands tend to swiftly wash out of tumor tissue, constraining the delivery of radiation doses from common therapeutic emitters such as lutetium or actinium. Consequently, scientists have been tirelessly developing novel ligand formulations to overcome this hurdle.