While PET MPI has seen increased interest among cardiologists, financial constraints and availability concerns have kept the modality from gaining traction in the US market.
The current set of radiopharmaceuticals has built-in drawbacks, but recent innovations could change that. 18F Flurpiridaz is a new agent is showing considerable promise – here’s what you need to know:
What is Flurpiridaz?
18F Flurpiridaz is a new PET MPI radiopharmaceutical that is still undergoing clinical development. It is a structural analog of pyridaben and binds to mitochondrial complex I with high affinity.
Flurpiridaz has specifically been developed as an agent for MPI PET imaging studies on those suspected of having CAD. At this stage of trials, Flurpiridaz is showing significant promise in terms of diagnostic efficacy.
How is Flurpiridaz changing Cardiac PET?
The biggest impact Flurpiridaz may have on cardiac PET is by making it more available. Current limitations on MPI PET come down to the radiotracers that are approved for use. Those tracers, N-13 labeled ammonia (13NH3) and O-15 labeled water (H215O) require facilities to have a cyclotron on the premises, an expensive and specialized piece of equipment that is not widely available. Flurpiridaz does not require the imaging center to have a cyclotron.
Facilities that don’t have a cyclotron may choose to use Rubidium-82 (Rb) which can be prepared on-site with a generator, however it is not ideal as an MPI PET tracer. For starters, it has a very short half-life of just 75 seconds, which makes it incompatible with exercise stress testing. If we compare this with Flurpiridaz, its 108-minute half-life gives more than enough time to conduct needed imaging, including exercise stress tests.
Secondly, Rb-82 has a long positron range that lowers image resolution. By comparison, the positron range of F-18 is approximately seven times shorter than that of Rb-82, which means it should produce images with much higher resolution.
Combining this with the longer half-life of Flurpiridaz means that it can provide more effective imaging with patients moving to the camera during stress testing. This provides the opportunity to detect milder perfusion defects and to more accurately quantify myocardial blood flow (MBF).
Lastly, as mentioned, Rb-82 requires a generator, whereas Flurpiridaz does not. Generators have high recurring costs, which is one reason why they are not widely available at medical imaging facilities.
Limitations of Rb-82
A Journal of Nuclear Cardiology study lists the following limitations of Rb-82:
- 82Rb PET MPI is only feasible with pharmacologic stress, as there is rapid decay of 82Rb activity and insufficient time to transfer the patient from a treadmill to the PET camera for post-exercise image acquisition.
- The rapid decay of 82Rb makes it impossible to repeat image acquisition in the event of patient motion. If severe patient motion artifact occurs on a peak-stress 82Rb image, it is necessary to repeat the pharmacologic stress infusion as well as the 82Rb infusion.
- The 82Sr/82Rb generator poses a large financial burden on the nuclear cardiology laboratory and limits 82Rb PET MPI to laboratories with sufficient patient volume to justify the high ongoing operating costs.
- Although 82Rb is an analog of potassium and is actively transported via the Na+/K+ATPase pump (like 201Thallium, a SPECT perfusion tracer with favorable myocardial uptake properties), the myocardial extraction fraction of 82Rb has been reported to be lower than that of other PET perfusion tracers. The lower myocardial extraction fraction leads to an earlier plateau in myocardial tracer uptake during vasodilator stress and an underestimation of the blood flow disparity between normally perfused and hypoperfused myocardial regions. The clinical implication is an underestimation of the extent and severity of CAD by 82Rb PET MPI.
- The positrons produced by decay of 82Rb are higher in energy than the positrons produced by other PET radionuclides, resulting in a longer positron range (the average distance traveled by a positron before interacting with an electron). The impact of the longer positron range of 82Rb is poorer spatial resolution of 82Rb PET images compared to images obtained using radionuclides with a shorter positron range (e.g., 13NH3 and 18F).
The bottom line is that Flurpiridaz represents lower costs, better usability and fewer requirements for expensive, specialized equipment. It can provide high-quality images, including during stress testing. These factors should help to make MPI PET more widely available to patients with suspected coronary artery disease.
What are the benefits of Flurpiridaz?
According to the company developing Flurpiridaz, Lantheus Holdings, it may be particularly useful for patients who are typically more difficult to obtain quality images from, including women and obese patients.
Additionally, with the ability for this to be produced at a central radiopharmacy and provided in the form of unit doses, most facilities with a PET scanner will have the option to offer this to patients, regardless of cardiac PET volumes.
“Based on clinical studies to date, we believe that in comparison to single photon emission computed tomography (SPECT) MPI, the current standard of care, PET MPI with 18F Flurpiridaz potentially provides:
- Higher image quality
- Increased diagnostic certainty
- More accurate risk stratification
- Reduced patient radiation exposure.”
We expect to see further reporting on clinical studies of Flurpiridaz somewhere around the middle of 2020. At the moment, it shows considerable promise as an agent that will help to improve the MPI PET process.