Not all PET scans are the same: why the tracer matters | Dr Dilanka De Silva

“Why do I need an FDG PET scan when someone else with cancer had a PSMA PET?”

It is a very reasonable question.

We often talk about “a PET scan” as though it is one test.

It is not quite that simple.

The PET scanner may be similar, but the radioactive tracer injected before the scan determines what biological process we are looking for.

That is why someone with lung cancer may have an FDG PET, while someone with prostate cancer may have a PSMA PET.

Understanding that difference makes the whole process much easier to understand.

Who is this article for?

This article may be helpful if:

• you have been told you need a PET scan;
• you are wondering why one type of PET scan has been chosen over another;
• you have questions about fasting or diabetes before a PET scan;
• you are worried about the radioactive tracer;
• you have prostate cancer and have been advised to have a PSMA PET; or
• you have more than one possible diagnosis and your doctors are deciding which scan will answer the right question.

A patient who prompted this discussion

I recently reviewed a gentleman with a particularly complex medical history.

He had previously been treated for multiple myeloma, including an autologous stem cell transplant, and had remained in remission for many years.

He had also previously been treated for prostate cancer with curative intent.

More recently, his CT scan showed new lung abnormalities and enlarged lymph nodes in the chest.

At the same time, his PSA had risen to 19.4 ng/mL, which clearly needed further assessment for possible recurrent prostate cancer.

There were several possibilities:

• inflammation or infection;
• a new lung cancer;
• recurrent prostate cancer; or
• recurrent multiple myeloma.

This is exactly the sort of situation where asking for simply “a PET scan” is not enough.

We first need to decide:

What question are we trying to answer?

The short answer

A PET scan shows us areas of abnormal biological activity in the body.

Most cancer PET scans are combined with CT imaging.

The PET component shows where the tracer accumulates.

The CT component shows us more precisely where those areas are anatomically.

Different tracers look for different biological targets.

So the best PET scan is not necessarily the newest scan.

It is the scan using the right tracer for the cancer we are trying to find.

What is a PET scan?

PET stands for positron emission tomography.

Before the scan, a small amount of a radioactive tracer is injected.

That tracer travels around the body and accumulates differently depending on the biological process it has been designed to detect.

The scanner then creates images showing where that tracer has accumulated.

This allows us to see information that a standard CT scan may not provide.

A simple way of thinking about it is:

CT shows us what something looks like.

PET can help show us how it is behaving.

Are PET scans radioactive?

Yes. A PET scan uses a small amount of radioactive material.

But the radioactivity does not remain in your body permanently.

The radioactivity fades naturally with time, and the tracer is gradually cleared from your body, often through the urine.

How quickly this happens depends on the particular tracer being used.

The nuclear medicine department may give you simple precautions to follow for a period after the scan, particularly regarding close contact with pregnant women or very young children.

The radiation exposure is carefully controlled, and your treating team weighs the expected clinical benefit of the scan against the radiation exposure.

The most common cancer PET scan: FDG PET

One of the most widely used tracers is:

18F-fluorodeoxyglucose, usually shortened to FDG.

FDG behaves in a similar way to glucose.

Many cancers use glucose at a higher rate than surrounding normal tissues.

FDG PET therefore allows us to identify areas with increased glucose metabolism.

It is commonly used in the assessment of cancers such as:

• lung cancer;
• lymphoma;
• melanoma;
• head and neck cancers;
• oesophageal cancer;
• selected breast cancers;
• multiple myeloma; and
• many other cancers.

But FDG uptake is not specific to cancer.

Infection and inflammation can also appear bright—or “hot”—on an FDG PET scan.

That is why the scan always has to be interpreted in context.

Why do I need to fast before an FDG PET?

This is specifically important for FDG PET because FDG behaves like glucose.

Current PET imaging guidance recommends fasting for at least 4 hours, ideally around 6 hours, before an FDG PET. Plain water is generally encouraged, although patients should always follow the instructions from their own imaging centre.

Patients are also commonly asked to avoid strenuous exercise beforehand because exercising muscles can take up FDG and make the images more difficult to interpret.

Keeping warm can also reduce uptake in a type of tissue called brown fat, which can sometimes interfere with interpretation.

What if I have diabetes?

Diabetes does not mean you cannot have an FDG PET scan.

But preparation is particularly important.

Blood glucose and insulin can both affect where FDG travels in the body.

The nuclear medicine team may therefore adjust the timing of the scan depending on:

• your blood glucose;
• whether you use insulin;
• when insulin was last given;
• other diabetes medications; and
• the type of diabetes you have.

The important message is:

do not change your insulin or diabetes medication yourself simply because you are having a PET scan.

Follow the instructions given by the PET department.

What does the PET report actually tell us?

When I review an FDG PET scan, I am interested in several things.

I look at:

• where the abnormal uptake is;
• what the area looks like on the CT component;
• whether there are other abnormal sites elsewhere in the body; and
• how strongly the tracer has accumulated.

You may see the term SUV, which stands for standardised uptake value.

SUV gives us a way of describing how much tracer has accumulated in a particular area.

But an SUV is not a cancer score.

A high SUV does not automatically mean cancer, and a lower SUV does not automatically mean something is benign.

The pattern, CT appearance, medical history and sometimes biopsy are all important.

FDG PET is not the right PET scan for every cancer

This is probably the most important point in the article.

Different cancers have different biology.

Some are very good at taking up FDG.

Others are better detected by tracers designed to bind to a particular molecule on the cancer cell.

Prostate cancer is the classic example.

What is a PSMA PET scan?

For many of the common clinical situations in prostate cancer, PSMA PET provides more useful information than FDG PET.

PSMA stands for prostate-specific membrane antigen.

It is a protein that is highly expressed by many prostate cancer cells.

A PSMA tracer is designed to attach to this protein, helping us find areas of prostate cancer that may be difficult to see on conventional scans.

PSMA PET is now used in appropriate patients with:

• newly diagnosed higher-risk prostate cancer;
• rising PSA after previous treatment;
• suspected recurrent disease; and
• metastatic prostate cancer.

Current European guidance recommends PSMA PET/CT, where available, for metastatic staging in high-risk prostate cancer and supports its use in unfavourable intermediate-risk disease.

How much better can PSMA PET be?

The Australian proPSMA trial included just over 300 men with high-risk prostate cancer.

For identifying lymph-node or distant metastatic disease:

• PSMA PET/CT had an accuracy of about 92%;
• compared with about 65% using conventional CT and bone scanning.

In patient language, that is roughly:

In that study, PSMA PET correctly classified about 92 in every 100 men, compared with about 65 in every 100 using conventional CT and bone scanning.

That was one of the studies that helped establish PSMA PET as such an important prostate cancer imaging tool.

Does PSMA uptake always mean prostate cancer?

No.

This is an important correction to a common misconception.

Despite its name, PSMA is not completely specific to prostate cancer.

PSMA uptake can occasionally occur in benign conditions and in other cancers, including some lung cancers, because PSMA may also be expressed in blood vessels associated with tumours.

So if a man with prostate cancer has a suspicious lung lesion, we cannot always say:

“It is PSMA-positive, therefore it must be prostate cancer.”

Depending on the situation, an FDG PET, dedicated chest imaging or biopsy may still be needed.

What about Copper-64 PSMA PET?

You may increasingly hear about Copper-64—or 64Cu—PSMA PET.

Copper-64 has a longer radioactive half-life than commonly used gallium-68 and fluorine-18 tracers. This may allow later imaging and make transport from a central production facility easier.

There is promising research into Copper-64 PSMA tracers, including studies investigating whether they may detect additional prostate cancer lesions in some situations.

However, I would be careful about describing Copper-64 PSMA as better than conventional PSMA PET at this stage.

The evidence is still evolving.

Standard gallium-68 and fluorine-18 PSMA PET remain established options, while Copper-64 PSMA is an emerging technology with more limited availability.

Comparing the PET scans

There are also other specialised PET tracers used for particular cancers and clinical questions.

The important point is that the tracer is chosen to match the biology we are trying to investigate.

Why my patient needed two different PET scans

Returning to my patient, there were really two separate questions.

The first was:

Could these lung abnormalities represent a new lung cancer, inflammation, or another process?

For that question, FDG PET was useful.

The second was:

Has his prostate cancer returned?

With a PSA of 19.4 ng/mL after previous definitive prostate cancer treatment, that possibility needed to be investigated.

For that question, PSMA PET was the more appropriate molecular imaging test.

One PET scan did not necessarily answer both questions.

That is the key lesson from his case.

PET scans do not always replace biopsy

PET imaging can tell us a great deal.

But it cannot always tell us exactly what an abnormality is.

Infection, inflammation and cancer can sometimes look similar.

Different cancers may also take up the same tracer.

When the diagnosis remains uncertain—and when knowing the exact diagnosis will change treatment—a biopsy may still be necessary.

Imaging helps us find and characterise the abnormality.

Pathology can tell us what the cells actually are.

What surprised me most

The interesting thing about PET imaging is that the machine itself is only part of the story.

What really changes the question we can answer is the tracer.

That is why asking:

“Which PET scan am I having, and what is my doctor trying to find?”

is often much more useful than simply asking:

“Do I need a PET scan?”

What does this mean for patients in Australia?

Medicare supports PET imaging for a number of defined indications through the Medicare Benefits Schedule, but not every PET scan is Medicare-funded in every clinical situation.

For prostate cancer, MBS items include PSMA PET for specified initial staging and recurrent-disease situations, and a separate PSMA PET indication relating to eligibility for lutetium-177 PSMA therapy.

FDG PET also has Medicare-supported indications across a range of cancers, with eligibility depending on the cancer type and clinical situation.

The nuclear medicine department can confirm whether a particular scan meets the current MBS criteria.

What would I usually consider?

Before choosing a PET scan, I would usually ask:

• What cancer are we looking for?
• What biological target does that cancer usually express?
• Are we staging a new cancer or looking for recurrence?
• What did the CT, MRI and blood tests already show?
• Will the scan result change treatment?
• Is more than one cancer diagnosis possible?
• Could we still need a biopsy after the scan?

The aim is not to order the most sophisticated PET scan available.

It is to choose the scan that answers the right clinical question.

The one message I want patients to remember

There is no single PET scan that is best for every cancer.

FDG PET looks mainly at glucose metabolism.

PSMA PET targets a molecule commonly expressed by prostate cancer.

Other tracers are designed to answer other biological questions.

Choosing the right PET scan can help us stage cancer more accurately, clarify where disease is located and decide what needs to happen next.

Key takeaways

• “PET scan” is a broad term. The tracer used determines what biological process the scan detects.
• FDG PET is widely used across many cancers, while PSMA PET is particularly useful in prostate cancer.
• A PET scan is not automatically diagnostic of cancer. Infection, inflammation and other diseases can also take up tracers.
• The best PET scan is the one that answers the specific clinical question, and in some situations more than one type of imaging—or a biopsy—may be needed.

Key evidence

1. Boellaard R, Herrmann K, Barrington SF, et al. [18F]FDG PET/CT: EANM procedure guidelines for tumour imaging: version 3.0. EANM J. 2025;1:100006. doi:10.1016/j.eanmj.2025.100006
2. Hofman MS, Lawrentschuk N, Francis RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet. 2020;395(10231):1208-1216. doi:10.1016/S0140-6736(20)30314-7
3. European Association of Urology. EAU Guidelines on Prostate Cancer. 2026 edition. Accessed June 26, 2026. https://uroweb.org/guidelines/prostate-cancer
4. Srinivasan R, Cook GJR, Patel N, Subesinghe M. Prostate specific membrane antigen (PSMA) avid nonprostatic benign and malignant disease: a pictorial review. Clin Radiol. 2024;79(9):639-656. doi:10.1016/j.crad.2024.05.013
5. Chen F, Zhang H, Zhan Y, et al. Preclinical and clinical evaluation of [64Cu]Cu-PSMA-Q PET/CT for prostate cancer detection and its comparison with [18F]FDG imaging. Sci Rep. 2025;15(1):14431. doi:10.1038/s41598-025-98757-8
6. Australian Government Department of Health, Disability and Ageing. Medicare Benefits Schedule item 61563. Accessed September 3, 2026. https://www9.health.gov.au/mbs/fullDisplay.cfm?q=61563&qt=item&type=item
7. Australian Government Department of Health, Disability and Ageing. Medicare Benefits Schedule item 61564. Accessed September 3, 2026. https://www9.health.gov.au/mbs/fullDisplay.cfm?q=61564&qt=item&type=item
8. Australian Government Department of Health, Disability and Ageing. Medicare Benefits Schedule item 61528. Accessed September 3, 2026. https://www9.health.gov.au/mbs/fullDisplay.cfm?q=61528&qt=item&type=item

Frequently asked questions (FAQs)

1. Does every PET scan use the same radioactive tracer?

No. Different PET tracers are designed to detect different biological processes.

2. Do I need to fast before every PET scan?

No. Fasting is particularly important for FDG PET. Preparation for other PET tracers may be different, so follow the instructions from your imaging centre.

3. Can I have an FDG PET if I have diabetes?

Yes. Diabetes usually requires additional planning around blood glucose, insulin and medication timing.

4. Does a “hot spot” on PET always mean cancer?

No. Infection, inflammation and some benign conditions can also show increased tracer uptake.

5. Is PSMA PET only used for prostate cancer?

It is mainly used clinically for prostate cancer, but PSMA uptake can also occur in some non-prostate conditions. The images therefore need expert interpretation.

6. Is Copper-64 PSMA better than a standard PSMA PET?

Not necessarily. It is a promising emerging tracer, but there is not yet enough evidence to say that it should replace established PSMA tracers for routine imaging.

7. Can a PET scan tell me for certain whether I have cancer?

Not always. Sometimes imaging provides enough information to guide management, but in other situations a biopsy is still needed.

About Dr Dilanka De Silva

Dr Dilanka De Silva is a Melbourne-based Medical Oncologist and Cancer Genetics Physician with experience in precision oncology, molecular imaging and complex cancer second opinions.

He completed fellowship training at Memorial Sloan Kettering Cancer Center in New York and reviews Australian and international patients, including patients from Sri Lanka, the Maldives, Indonesia and the Philippines.

Dr Dilanka De Silva
MBBS, MRCP(UK), MRCP(UK SCE Oncology), FRACP, PhD
Medical Oncologist & Cancer Genetics Physician
Memorial Sloan Kettering Cancer Center Fellow (New York, USA)