How PET scans detect cancer—and what the dark spots mean

PET scans detect cancer not by photographing a tumor or recognizing its shape, but by mapping where a chosen radioactive tracer accumulates in the body. The image therefore reflects a biological process rather than a simple anatomical picture.

That is the central difference between PET and computed tomography. CT mainly shows structure: the shape, density, and size of tissues. PET shows function, such as glucose use, receptor expression, or the activity of a particular cell population. The two are often combined as PET/CT so that one layer answers “where is the abnormality?” and the other helps show “what is happening there?”

How the image is produced

Before the scan, a small amount of a radiopharmaceutical is injected into the bloodstream. It contains a molecule designed to move toward a biological target and a radioactive label that emits positrons.

A positron soon encounters an electron. The two particles disappear, and their energy is released as two photons traveling in nearly opposite directions. Detectors surrounding the patient register these paired photons, and a computer reconstructs a three-dimensional map of the tracer’s distribution.

The more tracer a tissue accumulates, the more intense that region appears on PET. On grayscale whole-body projections, areas of high uptake are often shown as dark spots. On color displays, the same areas may appear yellow, red, or white. The color itself has no fixed meaning: interpretation depends on the display scale, the tracer used, and the signal relative to surrounding tissues.

The most widely used oncologic PET tracer is fluorodeoxyglucose, or FDG. It resembles glucose and accumulates in tissues that consume large amounts of sugar. Many tumors have high glucose use and therefore become visible on FDG PET.

High metabolic activity, however, is not the same as cancer. FDG normally accumulates in the brain and may also appear in muscles and other active tissues. Infection and inflammation can produce strong uptake, while some tumors take up relatively little FDG and remain difficult to see. A PET image cannot therefore be read as a simple map in which every bright or dark spot is malignant.

Different tracers reveal different biology

The scanner detects radiation, but the radiopharmaceutical determines what biological feature the image represents. One tracer can show glucose consumption, another can bind to a particular receptor, and another can label cells surrounding a tumor.

FAPI PET uses the third principle. FAPI stands for fibroblast activation protein inhibitor. It binds to fibroblast activation protein, or FAP, which is often present on activated fibroblasts within tumor stroma.

The stroma is not the cancer-cell population itself. It is the supporting tissue around the malignant cells, including connective tissue, blood vessels, immune cells, and fibroblasts. Tumors can recruit and reprogram these cells, which then remodel the extracellular environment, participate in signaling, and help sustain tumor growth. A FAPI tracer binds to FAP and can reveal areas where these fibroblasts are particularly active.

For that reason, saying that FAPI detects “the traces left by cancer rather than the cancer itself” is memorable but incomplete. The scan visualizes a real component of tumor tissue: its altered stroma. Some tumors have abundant FAP-positive stroma, others have much less, and activated fibroblasts are not exclusive to cancer.

What the well-known image actually shows

The image is a collection of whole-body PET projections from 15 patients with different histologically confirmed tumors. They came from a retrospective study of 80 patients that included 28 tumor types, 54 primary tumors, and 229 metastatic lesions.

The highest average FAPI uptake was reported in lung, breast, and esophageal cancers, cholangiocellular carcinoma, and sarcomas. Uptake nevertheless varied considerably among tumor types and even among patients with the same diagnosis. This distinction matters: one tracer visualized many cancers, but it did not perform equally in every cancer or establish the same diagnostic value in every setting.

Dark areas in the kidneys and urinary bladder mainly reflect tracer excretion. Benign conditions can also accumulate FAPI. FAP is expressed during wound healing, inflammation, and fibrosis, so uptake is not automatic proof of malignancy.

A physician therefore interprets the entire pattern rather than an isolated spot: its location, intensity, the corresponding anatomy on CT, the patient’s clinical history, and results from other tests. A biopsy may still be needed to establish a final diagnosis.

FAPI PET has not become a universal replacement for FDG PET. Its potential advantages depend on the tumor type and the clinical question, while broader routine use still requires standardized protocols, large prospective studies, and formal regulatory approval of the tracers.

FAPI PET illustrates the wider principle of molecular imaging. Disease can be visualized not only through the shape of a mass but also through a biological process occurring inside it or around it. PET does not automatically answer “is this cancer?” It shows the distribution of a selected target, and the meaning of that signal always depends on the tracer and the clinical context.