What FAPI Targets
FAPI stands for fibroblast activation protein inhibitor. Fibroblast activation protein (FAP) is found on cancer-associated fibroblasts, which are specialised cells in the tissue surrounding many types of tumours. These fibroblasts support tumour growth by creating a favourable environment for the cancer.
Unlike targets such as PSMA (specific to prostate cancer) or somatostatin receptors (prominent in neuroendocrine tumours), FAP is expressed across a broad range of cancer types. This makes FAPI a potentially versatile target for both imaging and therapy.
From Imaging to Therapy
The theranostic approach for FAPI follows the same principle as PSMA and DOTATATE. First, a FAPI PET CT scan is performed to see whether the tumour microenvironment expresses FAP. If the scan shows strong FAPI uptake at the tumour sites, it suggests that a therapeutic version of the FAPI molecule could reach those same sites and deliver targeted radiation.
Lu-177 FAPI therapy uses the FAPI-targeting molecule linked to Lutetium-177, which delivers beta radiation to the tumour-associated fibroblasts. By disrupting the tumour’s supportive environment and delivering radiation locally, the therapy aims to damage the cancer from the outside in.
Which Cancers May Benefit?
Because FAP is expressed in the stroma (supporting tissue) of many tumour types, Lu-177 FAPI therapy is being investigated for a range of cancers. Early research has focused on cancers where other targeted therapies have limited options, including pancreatic cancer, cholangiocarcinoma (bile duct cancer), certain sarcomas, and breast cancers.
It is important to understand that Lu-177 FAPI therapy is not yet a standard, widely approved treatment. Clinical research is ongoing, and its role in cancer care is still being defined through clinical trials and early experience.
How It Differs from PSMA and DOTATATE Therapy
While the theranostic principle is the same, there are differences. PSMA and DOTATATE target proteins directly on cancer cells, while FAPI targets proteins on the fibroblasts surrounding the tumour. Whether targeting the tumour microenvironment is as effective as targeting the cancer cells directly is one of the questions current research is exploring.
Another difference is the breadth of potential application. PSMA is largely specific to prostate cancer, and DOTATATE to neuroendocrine tumours. FAPI’s broader expression across tumour types could make it relevant for many more patients, but this broader applicability also requires careful research to determine where it works well and where it does not.
Current Status
Lu-177 FAPI therapy is in early clinical use and clinical trials at centres with expertise in radioligand therapy. Reports from early patients have been encouraging in some cancer types, but larger studies are needed to establish its effectiveness, optimal dosing, and safety profile more definitively.
If you are interested in whether FAPI-based theranostics could be relevant to your cancer, discuss it with your oncologist. They can advise whether your cancer type and situation make you a potential candidate and whether access to FAPI therapy is available at a nearby centre.