Exploring new research avenues

Researchers are addressing total-body kinetics for various diseases and benefiting from much higher PET sensitivity. The Biograph Vision Quadra™ PET/CT scanner was a major leap forward for clinicians at Royal North Shore Hospital and researchers from The University of Sydney in Australia.

Data courtesy of Royal North Shore Hospital, Sydney, Australia

In 2022, a new PET/CT scanner became necessary at Royal North Shore Hospital (RNSH), a large teaching campus of the University of Sydney Faculty of Medicine & Health. The previous PET/CT was over ten years old, and a new scanner was also deemed desirable from a research perspective. The nuclear medicine researchers were interested in a modern, long-axial field of view PET/CT scanner. Given this requirement profile, the decision was taken to upgrade to a Biograph Vision Quadra.

There are several aspects of Biograph Vision Quadra that make it attractive for researchers. First, the long-axial PET field of view allows for total-body imaging, seeing multiple regions simultaneously. “With a standard PET/CT camera, you can really only study one region of the body at a time,” says Professor Dale Bailey, head physicist in the RNSH Department for Nuclear Medicine and a former director of the Sydney Vital Northern Translational Cancer Research Centre. “You might study the liver, which would include the kidneys. But if you wanted to know what is going on in brain or in the muscles in the thigh, you wouldn’t be able to get that.” 

With total-body imaging, this becomes possible. Researchers can now look at their target organ and analyze how much radiopharmaceutical is extracted from the bloodstream in other parts of the body as well. This can provide new insights into various types of conditions, including cancer, neurological diseases, and other diseases. “It is like a video of what is going on in the whole body as opposed to taking a snapshot picture,” describes Bailey. 

The second highlight of Biograph Vision Quadra from a research perspective is the much higher PET sensitivity. Bailey explains, “You get about ten times more signal than with a standard camera.” A higher sensitivity allows for research protocols with less radiation dose, which is especially important in research with healthy volunteers. Higher sensitivity also makes it possible to follow tracers better. “With a standard camera, depending on the half-life of the radiotracer, you might be able to scan up to 24 hours after injection or administration. With Biograph Vision Quadra, you can go much longer, and so you get a better idea of the turnover of radiopharmaceuticals in the body.”

Once installed in mid-2023, Bailey and his team immediately embarked on various research projects that make use of Biograph Vision Quadra’s advantages—both in clinical research and in what Bailey calls “pure research.” Clinical research is focusing on patients. It is about disease dynamics in the body, and about the impact of specific therapies in individual patients. On the other hand, pure research is more diverse. It is about pharmacokinetics and pharmacodynamics, and also about basic (patho) physiology. 

Looking at the biodistribution of oxytocin is an example of an ongoing “pure research” project at RNSH that utilizes Biograph Vision Quadra. Oxytocin is a hormone that can potentially be used as an antidepressant. It is unclear whether it should best be administered nasally, orally, or intravenously. The researchers are now using radiolabelled oxytocin to analyze which works best.

A recent “pure research” publication of Bailey’s came into life more or less by chance. There was a debate going on in the European Journal of Nuclear Medicine and Molecular Imaging about whether the liver should be used as a reference in studies with Fludeoxyglucose injection F-18 (FDG), the most commonly used radiopharmaceutical in PET imaging. Based on mathematical modelling, experts from King’s College London pointed out that most of the FDG likely does not stay bound in the liver, making it not very suitable as a reference organ.¹ 

Bailey read that and was intrigued. He had not had that physiological research question in mind but having investigated total-body kinetics with Biograph Vision Quadra, he realized he could show how FDG is highly labile in the liver, entering the bloodstream, and redistributing to other organs. Bailey says, “I had data sets that could prove, with real images, what Kings College London colleagues had calculated mathematically.”

Bailey is very interested in how various types of tumors change as they migrate to other parts of the body. This can be different from region to region and from patient to patient, and it changes over time since the aggressiveness of a cancer tends to evolve. Ongoing clinical research at RNSH focusses on neuroendocrine tumors and prostate cancer, among other cancers. Bailey and his team are also looking into the radiobiology of radioembolization with selective internal radionuclide therapy (SIRT), a nuclear medicine cancer treatment with microspheres that carry Yttrium-90. SIRT is mostly used with liver cancer and liver metastases. Measuring dose distribution in this therapy with PET/CT is challenging. Bailey explains, “There is only a very small number of positrons produced by Yttrium-90 (around 3 ppm). We were the first to show that you can image that quantitatively and measure the actual radiation distribution. Now, with Biograph Vision Quadra, thanks to the high PET sensitivity, we are getting much better scans, and we can demonstrate the dose distribution in a very detailed manner.” 

Other types of radiotherapy are also of interest to study, and this too is currently being done at RNSH. It is unclear, for example, how best to deliver external beam radiotherapy to lung malignancies to limit damage to the healthy parts of the lungs. This can be addressed by Biograph Vision Quadra better than before—again thanks to its high PET sensitivity and a radioactive gas ([⁶⁸Ga]-Galligas) to demonstrate ventilation.

There are many more research projects on the horizon, including some that build on existing research done at the University of Sydney. Some years ago, RNSH researchers published using PET/CT as an alternative to biopsies in patients with temporal arteritis, a vascular disease that affects arteries that supply parts of the facial skull and eyes. Unless treated urgently, the disease can lead to permanent blindness. There is reason to believe that other vessels are also affected: the aorta, even the femoral arteries. “Thanks to the total-body scan of Biograph Vision Quadra, we will now be able to study that. This is a huge opportunity.”

Speeding up tumor imaging is another research area that Bailey will explore with their new total-body scanner. The usual thing to do in PSMA-imaging for prostate cancer, for example, is to inject the radiopharmaceutical and then wait for an hour until it has accumulated in the target tissue. At that time, a snapshot image is taken that shows the size of the tumor, its metastases, etc.

With Biograph Vision Quadra, this cumbersome routine might be replaced by a short dynamic-imaging protocol, in which images are acquired continuously during the first ten minutes after injection. Bailey explains, “This requires some additional modelling, but it should be feasible. The patients would go from the waiting room straight to the scanner and get their injection. And ten minutes later, they are finished.”

To finance their new scanner, an interesting sustainable cooperation model was developed. RNSH contributed part of the investment required and provided the clinical facility. The additional money came from a national research funding plan (the National Imaging Facility—NIF) and The University of Sydney. “What we proposed was a 50-50 split between clinical and research work. We do our clinical work in the morning—and in the afternoon, research takes over.” RNSH is still scanning its 15 to 20 routine clinical patients per day. But scanning with Biograph Vision Quadra, this work is finished by lunchtime. 

Quicker PET/CT examinations are not only helpful to free time for research. These examinations also increase patient comfort. Bailey shares a prime example for that. In patients with neuroendocrine tumors, but also in prostate cancer, dual PET/CT imaging can be very helpful clinically to understand the biology of an individual tumor. In dual PET/CT, a targeted tumor receptor imaging procedure is combined with an FDG-PET that provides information on tumor metabolism usually on consecutive days. 

Not anymore. With Biograph Vision Quadra, the dose of the first, short-lived receptor tracer can be reduced, and the second examination with FDG can be done the same day, in fact only a few hours later. No need to say that this is attractive, especially for patients who live far away from RNSH. To confirm this, Bailey and his colleagues conducted a survey among their patients, before and after the switch from the prior scanner to Biograph Vision Quadra. “The bottom line is: They love it. The satisfaction is much, much higher.”

Philipp Grätzel von Grätz lives and works as a freelance medical journalist in Berlin. His specialties are digitalization, technology, and cardiovascular therapy.