Published in Canadian Health Care Technology 29(4) May 2024
Although the nuclear medicine technology known as positron emission tomography (PET) has existed since the 1950s, technological advances in the last two decades have made PET imaging a game changer for cancer patients. PET is now imaging at the sub-cellular level and has become essential in guiding treatment for patients with many common cancers, including lung and lymphoma.
PET patients are injected with trace amounts of radiopharmaceuticals (radiotracers) and imaged in PET scanners, which look like computed tomography (CT) scanners.
Since the 1990s, the first routinely used PET radiotracer was a form of radioactive sugar – fludeoxyglucose F18, or FDG – which measures metabolic activity.
Many cancers crave more sugar as an energy source than normal tissues. This results in cancers sopping up more FDG and lighting up on PET images.
Four major advancements in PET technologies and radiotracers over the last decade have greatly benefited cancer patients.
Game changer 1 - PET significantly influences patient management:
Early results demonstrated FDG PET imaging significantly altered therapy – overall by about 27 percent, for many common cancers.
FDG PET imaging is especially useful for lung cancer. In 2002 Gambir et al. reported that lung cancer management changed in more than 40 percent of patients who had both FDG PET and CT imaging versus CT alone. FDG PET was more sensitive in demonstrating how far the lung cancer had spread and commonly demonstrated disease that was not seen on CT alone. Many patients avoided major surgery that would not have benefited them.
Very few imaging studies have had such an impact on cancer therapy. FDG PET imaging has become a standard of care for finding many common cancers, determining how far they have spread (staging), assessing response to treatment (prognosis) and monitoring patients for recurrence.
Game changer 2 - Hybrid imaging:
PET scanning demonstrates how the body functions (physiology) rather than what it looks like (anatomy). For example, CT and MRI imaging primarily demonstrate anatomy.
Both functional and anatomic imaging provide crucial information to guide patient management. It would be ideal to capture physiological and anatomic imaging in one technology. Enter the era of hybrid PET/CT and PET/MRI imaging technologies.
While training in nuclear medicine, I vividly remember swinging my head between FDG PET and CT scans to try to fuse them in my mind. It is important to know precisely where the PET abnormalities are. Is the FDG uptake in a blood vessel, a neighbouring lymph node, or something else? It makes a difference, and trying to fuse images with your eyes alone can be exhausting.
Around the mid-1990s, hybrid PET/CT scanners became commercially available and shortly thereafter became the standard configuration.
PET/CT hybrid units allow software fusion of PET and CT imaging, resulting in precise anatomic localization of pathology. You can view pure PET or pure CT images and anything in between. No more fusion with your eyes bouncing between PET and CT images on different displays. PET/MRI hybrid units came on the market around 2010. Although they demonstrated exquisite anatomy, especially in the pelvis or brain, they have not achieved significant market penetration.
In Canada, there has been a 19 percent increase in the number of PET/CT units over the last seven years, to a total of 56 units. The number of PET/MRI units has increased from two to six over the same time period; they are primarily used for research purposes (according to the CADTH Medical Imaging Inventory 2022-2023).
Game changer 3 - Precision medicine and the age of theranostics:
Theranostic radiotracers have two elements. One attaches to a specific cell structure, such as a surface receptor on the outer cell membrane, and the other carries a radioactive substance that can be swapped out for either imaging or therapy. Such diagnostic and therapy theranostic “pairs” have been developed for prostate and neuroendocrine tumours.
For example, a patient with advanced prostate cancer might be a candidate for Health Canada’s recently approved prostate cancer radiotracer treatment (marketed as Pluvicto by Advanced Accelerator Applications Inc.).
Before embarking on treatment, the patient should have two PET scans. The first is an FDG PET scan to demonstrate all the prostate cancer diseases. The second is prostate (68 Ga PSMA) PET, which will demonstrate prostate cancer cells that demonstrate specific cell receptors (i.e., prostate-specific membrane antigens or PSMA).
If the prostate-specific PET looks the same as the FDG PET scan, therapy can be entertained. If the FDG PET scan shows more disease than the prostate PET scan, the patient might not benefit from this therapy, as many of his prostate cancer cells will have lost their receptors and will not benefit from this treatment.
With theranostic agents, treatment is tailored at the individual patient level.
In a similar vein, there are theranostic agents for treating neuroendocrine tumours (e.g., 68 Ga DOTA for PET imaging and 177 Lu Octreotide for therapy).
Game changer 4 - PET/CT to guide therapy in advanced breast cancer:
Precision medicine, also known as personalized medicine, tailors therapy to individuals and their unique genetics and other characteristics and results in the“right treatments to the right patients at the right time.” (U.S. Food and Drug Administration)
Breast cancer is the second most common cancer in women, affecting one in eight and killing one in 34.
Breast cancer therapy is largely driven by cancer cell receptor status (e.g., estrogen, progesterone, and HER-2).
A study at Toronto’s Princess Margaret Hospital demonstrated that you cannot trust the receptor status of the original breast tumour to predict the receptor status of metastases. That’s why it is recommended that all cancer sites be biopsied.
However, in advanced breast cancer, biopsying every cancer site, especially if the cancer has spread to bone, is not always feasible.
A new FDA-approved PET estrogen receptor agent (Cerianna, marketed by GE HealthCare), solves this problem. This is a paradigm shift, as this is the first PET radiotracer to replace and complement invasive tissue sampling when biopsy is not feasible. There are no Health Canada-approved estrogen receptor agents at this time.
Again, an FDG PET scan will demonstrate all the disease, and the breast estrogen receptor PET scan will demonstrate how many cells have estrogen receptors. If much of the cancer has lost its estrogen receptor status, anti-estrogen therapy might not be beneficial, and alternate therapies can be considered.
After 20 years of being limited to FDG PET scanning, many new PET imaging agents are being developed and their use has expanded beyond cancer to include cardiology, neurology and inflammatory/infectious conditions.
PET technologies and novel PET radiotracers are leading the field of precision medicine.
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