What Is FAPI?
FAPI stands for fibroblast activation protein inhibitor. Fibroblast activation protein (FAP) is a molecule found on cancer-associated fibroblasts, which are cells in the tissue surrounding many types of tumours. These fibroblasts are part of the tumour’s microenvironment and play a role in how the cancer grows and spreads.
A FAPI PET CT scan uses a radioactive tracer that binds to FAP. Because FAP is present around many different tumour types, FAPI PET CT has potential applications across a broader range of cancers than some other specialised tracers.
Why FAPI Can Find Cancers That FDG Misses
FDG, the most commonly used PET tracer, works by detecting increased glucose metabolism. Most cancers consume more glucose than normal cells, making them visible on an FDG PET CT. However, some cancers have only modestly increased glucose uptake, which makes them harder to spot against the background of normal tissue.
FAPI works through a completely different mechanism. It targets the fibroblasts around the tumour rather than the tumour cells themselves. This means it can highlight cancers that are metabolically quiet on FDG but still have an active stromal (surrounding tissue) response.
Some specific advantages of FAPI PET CT include:
Low background uptake: Unlike FDG, which shows high uptake in the brain, liver, and urinary tract as part of normal metabolism, FAPI has very low uptake in most normal tissues. This creates cleaner images and makes it easier to spot tumours in areas where FDG creates confusing signals.
Better in certain organs: Tumours in the brain, liver, and biliary tract can be difficult to evaluate with FDG because of high background activity. FAPI often provides much clearer contrast in these locations.
No fasting required: Because FAPI does not depend on glucose metabolism, patients do not need to fast before the scan. This can be an advantage for patients with diabetes or those who have difficulty fasting.
Which Cancers Can FAPI Help With?
Research has shown promising results for FAPI PET CT in several cancer types. These include pancreatic cancer, cholangiocarcinoma (bile duct cancer), gastric cancer, certain sarcomas, and some breast cancers. It has also shown value in hepatocellular carcinoma (liver cancer), where FDG can be less reliable.
FAPI is not a replacement for FDG in all situations. For cancers where FDG performs well, such as lung cancer and lymphoma, FDG remains the standard first-line tracer. FAPI is most valuable when FDG has limitations for a particular cancer type or when additional information is needed.
FAPI in Theranostics
Just as PSMA can be used for both imaging and therapy in prostate cancer, FAPI is being explored as a theranostic target. If a FAPI PET CT confirms that a tumour’s microenvironment expresses FAP, a therapeutic version of the FAPI molecule carrying a treatment dose of radiation (such as Lu-177 FAPI) could potentially be used for treatment.
This application is still in the early stages of clinical research, and it is not yet a standard treatment. However, the theranostic potential of FAPI is an active area of investigation that could expand treatment options for several difficult-to-treat cancers in the future.
Is FAPI PET CT Right for You?
The decision to use FAPI PET CT rather than, or in addition to, FDG PET CT depends on the clinical question being asked. Your oncologist and nuclear medicine physician will consider the type and location of your cancer, what information is needed, and what other imaging has already been done.
If you have been told that your cancer is not clearly visible on FDG PET CT, or if your doctor is looking for additional information to guide treatment, ask whether a FAPI PET CT could be helpful in your situation.