Next-level theranostics 
with total-body PET/CT

After three decades in academia, an Australian nuclear medicine pioneer has launched a new theranostics center in Melbourne. With his Biograph Vision Quadra™ PET/CT scanner, he is not only aiming to improve the patient experience, but he also wants to advance early clinical research into novel radiopharmaceuticals and thus help to broaden the spectrum of theranostics for cancer care.

Data courtesy of Melbourne Theranostic Innovation Centre, Melbourne, Australia

When Professor Rod Hicks left Peter MacCallum Cancer Centre at Melbourne University at the end of 2021, he had gained more than 30 years of experience in nuclear medicine, PET imaging, and radionuclide therapy. For three decades, Hicks had been a major driver of the university’s theranostics program. “Peter Mac,” as many call the cancer center, is today among the leading centers in the world for research and clinical nuclear medicine.

But all good things come to an end, and so did Hicks’ work at Melbourne University. He quips, “Probably the most stupid thing I could have done is to launch a research and development company when I should be retiring after thirty years in the public healthcare system.” Hicks did that most seemingly irrational thing, and he founded the Melbourne Theranostic Innovation Centre (MTIC) in March 2022. At the core of it is a Siemens Heathineers Biograph Vision Quadra PET/CT scanner.

Why found a company when it is the time many are considering retirement? The PET/CT scanner played an important part in that decision. “The opportunity to get a Biograph Vision Quadra was too tempting for me,” says Hicks. The scanner was installed in January 2023, and MTIC started clinical operations on Valentine’s Day, February 2023. Professor Hicks says that he fell in love with the system at first sight of the scan from patient number one!

The attractive research environment at a private research company was another reason for starting anew. “Early clinical trials have become difficult in a busy clinical environment. With many patients on the clinical waiting list in public hospitals, it is hard to justify taking the camera to do the multi-time-point imaging that you need for radiation dosimetry estimations, or the delayed imaging that is necessary in clinical trials of new therapeutic agents.”

MTIC, which has strong research partnerships with local and international biotechnology companies, blends its routine clinical work with research, leveraging the former to identify patients suitable for the latter. “What we are offering is a combination of clinical services and early phase clinical research and development of novel theranostic agents,” says Hicks. The clinical trials, in turn, aim at developing new theranostic cancer care pathways. One way to do that is by establishing and validating new radiopharmaceuticals that act as companion diagnostics for therapies in the pipeline. Hicks is very keen on these kinds of trials, and the first three are already under way. Another focus area is optimizing existing diagnostic and therapeutic processes—with the help of a scanner that features a long axial field-of-view and a sensitivity that is on average about ten times higher than that of most other PET/CT scanners.

During 2023, Hicks and his team built their clinical network, since no theranostics center can exist without close cooperation with oncologists, surgeons, radiation experts, and many other specialists. MTIC has seen keen interest from the local medical community. “The unique capabilities of Biograph Vision Quadra are very attractive both for patients and referring clinicians.” A key clinical field for MTIC is prostate cancer care. In fact, the MTIC facilities are located on the same floor as the Australian Prostate Centre, a unique medical facility dedicated exclusively to the treatment of men with prostate cancer, providing a holistic approach that includes psychological support and a exercise program supervised in-house by physiotherapists.

What Biograph Vision Quadra can offer to prostate cancer patients is the opportunity to do dynamic imaging that is both fast and highly sensitive. Hicks and his team have used both ¹⁸F-DCFPyl PSMA and ⁶⁸Ga PSMA-11 as prostate cancer tracers. “With 10-minute dynamic imaging, we get a very early visualization of sites around the bladder, especially in the prostate bed.” Hicks explains that this is particularly good for identifying recurrences at the anastomoses of urethra and bladder and for detecting recurrences in the seminal vesicle pedicles and close to the ureters, which become obscured when there is high urinary activity.

As an added bonus, the whole-body scan also provides information about cardiac function, about thromboembolic events, and about asymmetries in renal perfusion—all of which is information that is good to have for any cancer patient, and specifically so in prostate cancer patients. “We really find this scanner extraordinarily useful for prostate cancer,” states Hicks.

Another area that illustrates how Biograph Vision Quadra can lead to new and very patient-friendly theranostic cancer care pathways is dual-isotope imaging. In patients with prostate cancer—PSMA-based tracers localize the tumor, while glucose-based tracers like fludeoxyglucose injection F 18 (FDG)^[a] provide information about the metabolism and thus the aggressiveness of the cancer.

Neuroendocrine tumors are another cancer type in which tracer combinations are regularly used, says Hicks. “In these patients, we sometimes even use three different tracers to characterize the disease properly.”

To illustrate what dual-isotope imaging actually means from a patient and care pathway perspective, Hicks tells of a prostate cancer patient where both PSMA and FDG imaging were deemed necessary. In institutions with a conventional scanner, these examinations tend to take place on two consecutive days. This can mean staying overnight in a hotel for a patient who does not happen to live nearby. “Using Biograph Vision Quadra, we did this imaging within three and a half hours.”

Specifically, Hicks started the examination with injecting 0.5 MBq/kg PSMA tracer. “This is a very low activity, thanks to the high sensitivity Biograph Vision Quadra provides.” The first step was a dynamic imaging, followed by another scan after one hour for the biodistribution. Then came the FDG tracer, applied at a higher activity of 2 MBq/kg. For the FDG imaging, the initial PSMA scan was subtracted from the combined FDG/PSMA scan. In the end, both scans were available without interference—and with no more radiation than would have usually been applied during a two-day protocol. These sophisticated acquisition protocols are being complemented by tools MTIC is helping to the develop in the artificial intelligence (AI) domain.

When it comes to clinical research, there are at least three clinical trials that Hicks and his team are recruiting throughout 2024. They primarily address cancer types far beyond prostate cancer, and the studies use radiopharmaceuticals other than PSMA or FDG. The first of these trials looks into melanoma. It uses a novel imaging agent that is directed against a molecular target involved in the formation of the pigment melanin. Melanin-PET-imaging has been reasonably specific for melanoma cells in preclinical models. It could thus be used to image melanoma recurrences or metastases in patients. There is also a therapeutic tracer available, and it looks promising in preclinical research, as well, says Hicks: “We hope that, provided trials of the diagnostic agent are successful, we will be able to translate that into a therapeutic trial.”

The second trial that is being initiated at MTIC is looking at an agent against a target expressed in various urothelial malignancies, and also in renal cancer and, to a lesser extent, in breast and ovarian cancer. Here, too, a therapeutic agent would be available so that new theranostic care pathways for different types of cancer are at least a possibility. The third current MTIC trial is particularly interesting in that it uses a dual-targeting agent. The radiopharmaceutical is directed against two targets expressed by pancreatic cancer, a type of cancer for which therapeutic options are extremely limited.

The main promise or vision of MTIC and its Biograph Vision Quadra-based research program is to extend the scope of the targeted and well-tolerated theranostic approach beyond classical application areas like prostate cancer, neuroendocrine tumors, and thyroid cancer. Hicks says, “The challenge is not so much the availability of targets. There are many. The challenge is getting the radiopharmaceuticals approved. This needs robust biodistribution and dosimetry data, and a clear demonstration that the chosen target is a valid therapeutic option.”

Biograph Vision Quadra, according to Hicks, might make it possible to perform early clinical trials that could even test two or indeed three compounds in the same patient, allowing them to act as their own control. This could be performed without increasing the radiation dose beyond that with a single tracer on a conventional PET/CT. The benefits for tracer development are clear, especially for studies including healthy volunteers. Studies like this would have the potential to accelerate research and development substantially. “These are really exciting times in nuclear medicine research. While I loved my involvement in the field for the last 30 years or so, I think that the next generation entering the field will have an even more amazing opportunity to impact health outcomes positively. I encourage young clinicians to get involved in the theranostic revolution.”

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