PET in cancer care: what the scan can and cannot answer

A cancer diagnosis tends to raise a short list of practical questions. How far has it spread? Is the treatment working? Has it come back? PET, short for positron emission tomography, is one of the imaging tools doctors use to help answer them. It is rarely used alone, and it does not suit every cancer. This page explains what a PET scan in cancer care measures, the main ways it is used, why some tumours are hard to see, how other tracers extend the method, and the real limits of the technique.

We use FDG as the running example because it is by far the most common tracer in oncology. If you want the wider picture of how tracers work, see PET radiotracers explained.

What an FDG-PET scan actually measures

FDG (fluorodeoxyglucose) is a glucose analogue, a sugar-like molecule given a radioactive label. Cells that use a lot of glucose take up more of it, and the scanner maps where the signal collects. A review of how oncologic scans are read describes the technique's key strength as its ability to measure glycolytic metabolism non-invasively (Hofman and Hicks, Cancer Imaging, 2016). In plain terms, a CT or MRI mainly shows shape and size, while FDG-PET adds a picture of activity.

That activity is not unique to cancer. European guidelines note that increased FDG uptake appears in many tumours, but also in healing tissue, infections and other inflammatory processes (Boellaard and colleagues, EANM procedure guidelines, 2014). Keep that sentence in mind. Much of what follows depends on it.

Most oncology scans today are PET-CT, where a CT scan is taken in the same session so the activity can be placed on the anatomy. The reasons for combining them are covered in PET-CT and PET-MRI, why scanners are combined.

Staging: finding out where the disease is

Staging means working out how far a cancer extends: the original tumour, nearby lymph nodes, and distant sites. PET-CT is used for this because a whole-body scan can reveal active disease in places that were not the focus of earlier tests. RadiologyInfo.org, the patient site of the RSNA and ACR, lists finding out whether cancer has spread among the main uses of the scan (RadiologyInfo.org).

Lymphoma is a good example of where FDG-PET has become routine. A 2022 review of the Lugano classification, the system used to stage and assess lymphoma, states that FDG-PET/CT has become the standard for staging and response assessment in Hodgkin lymphoma and FDG-avid non-Hodgkin subtypes. The same review reports that PET/CT is the preferred imaging method for staging these lymphomas compared with CT, particularly for finding disease outside the lymph nodes (Yoo, Blood Research, 2022). Note the word "avid" there. It matters, and we return to it below.

Assessing response to treatment

A repeat scan during or after treatment lets specialists compare the pattern of uptake with the scan taken before treatment began. In lymphoma, a five-point visual scale called the Deauville scale is used: a score of 1 means no uptake, while 5 means markedly increased uptake compared with the liver, or new lesions (Yoo, 2022). It is one disease-specific example of how a pattern of uptake is turned into a shared language between doctors, not a general scoring system for all cancers.

Comparison with the baseline scan is central. Hofman and Hicks note that comparison with prior studies is critical to answering the clinical question, and that errors can occur if a scan is compared only with the most recent one. A series of scans too close together can make a finding look stable when the baseline would show clear progress or regression (Hofman and Hicks, 2016). In practice, this is one reason centres give precise preparation and timing instructions (see what to expect on scan day).

Looking for recurrence

Checking whether cancer has returned after treatment is one of the standard uses listed by RadiologyInfo.org (RadiologyInfo.org). The reasoning is simple: activity that has reappeared can show up on PET even when the anatomy on CT or MRI is hard to read.

The limits matter here too. Healing tissue and inflammation also take up FDG, so a spot in an area that was recently treated is not automatically a recurrence. When to scan after treatment, and how to read what is found, is a judgement for the care team.

Why some cancers are harder to see

"FDG-avid" means a tissue takes up FDG strongly enough to stand out from its surroundings. Not every cancer does. A teaching review in Radiographics describes malignancies with low FDG uptake and gives the main reasons: tumours with low glucose metabolism or low cellularity, improper patient preparation, and small tumour size. Examples it discusses include low-grade lung adenocarcinomas, renal cell cancers and mucinous neoplasms (Flavell and colleagues, Radiographics, 2016).

Hofman and Hicks add that some aggressive sarcomas and mucinous tumours can appear PET-negative when the signal from cancer cells is diluted by adjacent mucin or extracellular matrix. Small lesions and areas that move with breathing can also look fainter than they are. The reverse happens as well: certain benign growths, such as uterine fibroids and some breast fibroadenomas, can show fairly high FDG uptake (Hofman and Hicks, 2016).

This is why a negative FDG scan does not by itself prove that no cancer is present, and why doctors choose the imaging method to suit the cancer. For a tumour type that does not take up FDG well, another test or another tracer may be more useful.

Other tracers: PSMA and somatostatin receptor imaging

Different tracers target different biology. Two well-known examples illustrate the idea.

PSMA tracers bind to prostate-specific membrane antigen, a protein found at high levels on most prostate cancer cells. A joint EANM and SNMMI guideline says PSMA is not specific to prostate tissue despite its name, and that around 5 percent of prostate cancers, especially neuroendocrine types, do not show significant PSMA expression. It also reports that in the phase III ProPSMA trial, Ga-68 PSMA-11 PET/CT was 27 percent more accurate than CT plus bone scan for staging people with newly diagnosed high-risk prostate cancer (Fendler and colleagues, EJNMMI, 2023). That is one trial in one setting, so it should not be generalised to every patient. The guideline's listed uses include locating prostate cancer when the blood PSA level rises after treatment.

Somatostatin receptor tracers work on a similar principle for neuroendocrine tumours that carry somatostatin receptors. In June 2016 The ASCO Post reported the US FDA approval of the first kit for preparing Ga-68 dotatate, an agent to help locate somatostatin receptor-positive neuroendocrine tumours in adults and children. The same report cautions that uptake can also occur in other tumour types or conditions, so tissue sampling or other assessments may be needed to confirm what a hot spot is (The ASCO Post, 2016).

Availability of these tracers varies by country and centre. Whether one is suitable for a particular person is a decision for their oncology team.

False positives, and why PET is read alongside other tests

A false positive is a spot that lights up on the scan but turns out not to be cancer. The commonest culprits are inflammation and infection, which the EANM guidelines list alongside healing tissue as causes of increased FDG uptake. Some benign growths can look similar to tumour on the PET images alone.

Two safeguards reduce the risk. The first is the CT or MRI that accompanies the PET. Hofman and Hicks stress that integrating anatomic information from CT is important for accurate interpretation because it can improve both the specificity and sensitivity of PET findings. The second is clinical history: what treatment you have had, when, and what symptoms or blood tests are relevant (Hofman and Hicks, 2016). A reading specialist who knows you had pneumonia last month will weigh a lung spot differently from one who does not.

Sometimes the answer is still unclear, and a biopsy or a follow-up scan is the sensible next step. That is a normal part of the process, not a sign that something went wrong. For the vocabulary used in the written result, see reading a PET report.

A role in radiotherapy planning

Radiotherapy aims radiation at a defined target, so the team has to decide where the tumour starts and stops. PET can help with that. An IAEA consensus report on lung cancer radiotherapy recommends FDG-PET/CT as an essential part of planning for curative-intent treatment of non-small cell lung cancer. It notes that PET reduces variation between observers in outlining the target and that PET-based outlines are on average smaller than those drawn without PET, which can spare nearby healthy tissue. It also notes that distinguishing collapsed lung from tumour is easier with PET (Konert and colleagues, Radiotherapy and Oncology, 2015).

The same report is frank about constraints. PET has a resolution of roughly 4 to 8 mm, scans taken in a different body position are hard to line up with the planning CT, and low-uptake tumours are harder to outline. It recommends that a radiation oncologist and a nuclear medicine physician review the images together, and that automatic outlining is not used without a human check. This report concerns lung cancer specifically, so other cancers have their own guidance.

Honest limits

PET has real boundaries. Resolution is lower than CT or MRI, so very small deposits can be missed. RadiologyInfo.org notes the image resolution may be lower than CT or MRI, even though PET is more sensitive for many indications, and that high blood sugar or insulin levels can affect the results (RadiologyInfo.org). Numeric measures such as SUV, the standardised uptake value, vary with the scanner, the preparation and the timing, which is why they are used as supporting evidence rather than as verdicts. Guidelines recommend a 60 minute interval between injection and scanning, with an accepted range of 55 to 75 minutes (Boellaard and colleagues, 2014).

Radiation is a consideration, too. The doses involved are weighed against the value of the information, and that balance is discussed in radiation dose in context. Finally, PET gives a snapshot. It cannot say how a cancer will behave over years, and it cannot replace a pathology report from tissue.

The short version

In cancer care, FDG-PET adds information about activity to the shape and size shown by CT and MRI, and it is used for staging, judging treatment response, finding recurrence and sometimes planning radiotherapy. It works best for FDG-avid cancers and is weaker for tumours that take up little sugar. Because inflammation can mimic disease, the result is always read together with other imaging and your history, and the final interpretation belongs to your own imaging and treating teams.