Flurpiridaz, a novel positron emission tomography (PET) cardiac radiotracer is poised to make a major impact on nuclear cardiology. Experts in cardiac imaging say it offers much better imaging than SPECT, the current cardiac nuclear imaging workforce technology. It can be made by commercial cyclotrons and has a much longer half-life to make it available in on-demand doses that can be ordered and transported to the hospital. This may deliver a much more economic option for PET to expand, as opposed to the current standard of expensive rubidium-82 generators.
The results of the flurpiridaz FDA pivotal trial, AURORA (International Study to Evaluate Diagnostic Efficacy of Flurpiridaz [18F] Injection PET MPI in the Detection of Coronary Artery Disease [CAD]), were published Oct. 9 in the Journal of the American College of Cardiology.[1] The phase 3, prospective, open-label, international, multicenter study of flurpiridaz for PET myocardial perfusion imaging (MPI) in patients with suspected CAD showed excellent results. It was compared with the current standard of care of SPECT with the radiotracer technetium-99m. The results showed flurpiridaz significantly exceeded prespecified threshold criteria for the detection of CAD and was superior to Tc-labeled SPECT MPI for the detection of CAD in the overall population and in women and obese patients.
These findings have paved the way for the anticipated approval of flurpiridaz by the U.S. Food and Drug Administration (FDA). GE Healthcare, the manufacturer of flurpiridaz, has submitted the results to the FDA for final review.
"Undoubtedly, publication of the AURORA trial is a milestone in nuclear cardiology. Publication of the AURORA trial is an important step toward FDA approval of flurpiridaz, which has a longer half-life than currently available radiopharmaceuticals. This advantage would allow unit dosing and exercise testing," explained American Society of Nuclear Cardiology (ASNC) President Mouaz Al-Mallah, MD, Mac, MASNC, in a letter to members on Oct. 10.
Flurpiridaz was one of the hottest topics at the annual ASNC meeting in 2022 and again in 2023.
Timothy Bateman, MD, co-director of the cardiovascular radiologic imaging program at Saint Luke's Mid America Heart Institute, professor of medicine at the University of Missouri-Kansas City School of Medicine and an ASNC past-president, is a co-author on the AURORA study. He spoke with Cardiovascular Business about his group's findings and what it is like to work with flurpiridaz.
"It was a very high quality study. It was carried out at a lot of centers across the U.S. and Canada and Europe. The study did meet its primary endpoints. It met its secondary endpoints. I do think it is time for practices at the many hospitals that are not offering cardiac PET to be thinking about what this means," Bateman said.
For hospitals that have been on the fence about investing in PET imaging systems, the expected FDA clearance of flurpiridaz may be the missing piece of the puzzle that pushes many to make the investment. Bateman said facilities still need to plan ahead to line up funding and begin planning for an install.
"Those of us who have done this for years have learned that that's a one- to two-year type business proposition. One of our initiatives through ASNC and Society of Nuclear Medicine and Molecular Imaging (SNMMI) is to begin encouraging people to understand what this agent is all about," Bateman explained.
Why flurpiridaz is a game-changer in cardiac imaging
There are several key advantages that set flurpiridaz apart from existing radiopharmaceuticals. First, it has a longer half-life compared to currently available agents. This prolonged half-life facilitates unit dosing and exercise stress testing, offering clinicians greater flexibility and precision in diagnostic procedures. This alone represents a significant advancement in PET imaging.
"That's a tremendous advance for the expansion of PET into the marketplace. The problem is that the penetration of PET into the broader community has been limited because you must have a hefty volume of patients on a daily basis to mitigate the risk of signing a contract for a rubidium generator that is very costly on a monthly basis," Bateman said.
He said there are lots of studies and meta-analyses showing that PET is better than SPECT. It has better diagnostic accuracy, sensitivity and specificity, for example, as well as being associated with better image quality, more definitive interpretations and more confident interpretations. It is also much more accurate in particular subpopulations, like obese patients and women, where its has been shown to be superior over SPECT.
Being able to now order a unit dose from a commercial cyclotron and have it delivered is a major business game-changer.
"If you've got some patients, you order the tracer. So the risk has been switched, if you want to put it that way, from the provider to the manufacturer. This is an exciting time for people like me who have been practicing nuclear cardiology for quite some time. We haven't had any new tracers since the early 1990s. That's a long time ago. And along comes this flurpiridaz that has some very, very excellent characteristics. Not only is it a PET agent, but it's also got a high extraction rate, particularly at high flows, which should substantially improve sensitivity. It's a fluorinated F18 tracer. All of our PET cameras are designed specifically to be able to elicit excellent F18 images," Batman said.
Flurpiridaz's high extraction rate enhances sensitivity in detecting CAD. This characteristic ensures that even patients with more advanced or subtle forms of the disease can be accurately diagnosed. The tracer's uptake by mitochondria in cells and its prolonged retention ensures that it does not redistribute, a critical feature for reliable and reproducible imaging, Bateman added.
One of the most remarkable aspects of flurpiridaz is its extended half-life of approximately 110 minutes. This attribute allows for stress testing with either pharmacological agents or exercise, offering clinicians more options in tailoring diagnostic procedures to individual patient needs. With traditional agents like rubidium, which have very short half-lives (about 75 seconds), exercise stress testing is often not feasible due to the limited time available for imaging. Flurpiridaz's extended half-life mitigates this limitation, providing healthcare providers with a versatile tool for cardiac stress testing.
Flurpiridaz's longer imaging window not only improves the overall image quality but also offers the opportunity to detect CAD at earlier stages, Bateman said. This is particularly significant as it allows for the identification of spatially relative perfusion defects, even before they reach the severity of traditional ischemic defects. In clinical practice, this means that physicians can potentially diagnose CAD in patients who may not exhibit severe symptoms or clear-cut perfusion defects, a capability that can significantly impact patient outcomes.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com