FAPI PET/CT: where it earns its place over FDG

FDG has been the workhorse of oncologic PET for three decades and will remain so. But every reporting radiologist has a mental list of the situations in which it disappoints, and that list has been fairly stable for years: pancreas, stomach, liver, biliary tract, peritoneum, and anything sitting against a high-background organ.

68Ga-FAPI addresses a good part of that list, and this note is a practical summary of where we find it useful.

The mechanism, briefly

FAPI targets fibroblast activation protein, a serine protease expressed by cancer-associated fibroblasts in the tumour stroma rather than by the malignant cells themselves.

That distinction is the whole point. In desmoplastic tumours — pancreatic adenocarcinoma being the archetype — stroma can constitute the majority of tumour volume. Imaging the stroma therefore images the tumour, and it does so without depending on glycolytic rate.

The corollary is uniformly low physiological background. Normal brain, liver, muscle and bowel express little FAP. Tumour-to-background ratios are consequently high even where the absolute uptake value is moderate.

Where we find it changes management

Pancreatic and biliary malignancy. The combination of low intrinsic FDG avidity in some tumours and high background pancreatitis-related uptake makes FDG unreliable here. FAPI delineates the primary and, more usefully, peritoneal and nodal disease that alters resectability.

Peritoneal carcinomatosis. This is the clearest gain in our experience. Thin sheets of peritoneal disease that CT calls indeterminate and FDG under-reads become conspicuous. For patients being considered for cytoreductive surgery, the difference is a genuine change in surgical candidacy.

Gastric and signet-ring / mucinous adenocarcinoma. Classically poorly FDG-avid. FAPI is not defeated by low glycolysis.

Hepatocellular carcinoma and liver metastases. High physiological hepatic FDG uptake is the limiting factor. Low hepatic FAP expression removes it.

Brain tumours. Cortical glucose metabolism makes FDG close to useless for many intracranial lesions. FAPI's negligible background changes that.

Head and neck, post-treatment. Distinguishing post-radiotherapy inflammatory change from residual tumour remains genuinely difficult on FDG. FAPI is less confounded, though not immune — see the caveats.

Diabetic and hyperglycaemic patients. No fasting, no blood sugar dependence. For patients in whom FDG imaging is simply unreliable, this is decisive rather than merely convenient.

Practical points

• No fasting, no glycaemic preparation. Worth stating explicitly to patients, who arrive expecting the FDG protocol.
• Uptake time is shorter than FDG — imaging is feasible from around 10 minutes, though we generally acquire later for better clearance and, where the question is peritoneal, consider delayed imaging.
• Tracer is produced to order. Booking needs a few days' notice; we schedule FAPI slots in batches against generator elution.
• Dosimetry is favourable relative to FDG in most published series.

Caveats worth stating to referrers

FAPI is not tumour-specific. FAP is expressed in any process involving activated fibroblasts, which means:

• Fibrosis and healing tissue — post-surgical scars, radiotherapy fields, healing fractures.
• Chronic inflammation, including pancreatitis, IgG4-related disease and fibrosing conditions.
• Myocardial remodelling and hepatic fibrosis in the appropriate clinical context.

In a country with a high tuberculosis burden, the granulomatous differential deserves the same respect it gets with FDG. FAPI avidity is not a synonym for malignancy, and reports should not be written as though it were.

We also caution against reading FAPI in isolation where an FDG study exists. The two are complementary; discordance between them is informative rather than confusing, and in several of our cases the combination has been more useful than either alone.

How to refer

FAPI is appropriate when there is a defined clinical question that FDG has failed to answer, or where FDG is predictably unreliable in the tumour type concerned. It is not a general-purpose upgrade to a staging scan, and we would rather discuss a case before booking than report a study that was never going to change management.

If you have a case you would like to talk through, call +91 93169 25516 or bring it to the weekly tumour board. We are happy to look at prior imaging before committing a patient to the study.

References worth reading

The Heidelberg group's original characterisation papers remain the best starting point, along with the growing body of comparative FAPI-versus-FDG series in gastrointestinal and peritoneal malignancy. Indian availability remains limited, and the literature is still maturing — we report these studies with that context in mind and say so in the report when the evidence base for a particular indication is thin.