Flurpiridaz

Flurpiridaz

Thallium was once the gold standard agent for myocardial perfusion imaging. Now it has been largely supplanted by technetium mainly because of the ease of handling as thallium has a very short half life. Flurpiridaz, an F-18 based agent for positron emission tomography is set to revolutionize myocardial perfusion imaging once again. Some of the limitations of single photon emission computed tomography (SPECT) imaging of the heart are the potential for artifacts due to soft tissue attenuation, activity of proximal gut, image quality and the limitation due to first pass myocardial extraction. Myocardial perfusion positron emission tomographic images have higher spatial resolution and has the benefit of more precise attenuation correction.¹

Flurpiridaz F-18 is slated to be an ideal myocardial perfusion imaging agent for positron emission tomography (PET). Flurpiridaz F-18 binds to the mitochondrial complex I with high affinity, has high cardiac uptake gives clear delineation of perfusion defects. The tracer uptake into the myocardium is rapid and the retention is prolonged. Flurpiridaz F-18 uptake into adjacent tissue is low. The myocardial extraction profile is superior to that of Thallium 201 and 99m Technetium sestamibi.²
Preclinical and phase I clinical trials had shown idealistic features of an imaging agent for flurpiridaz F 18. Last year a phase II trial has documented the safety and superiority of flurpiridaz F 18 over SPECT in terms of image quality, certainty of interpretation and overall diagnosis of coronary artery disease with luminal narrowing of 50% or more.³ Study drug related adverse effects were noted in only three of the one hundred and thirty two patients. The adverse effects noted were transient hypotension, mild cough and a metallic taste. All adverse effects resolved without any complications. Radiation dose noted with flurpiridaz F 18 was lower than conventional 99m Technetium SPECT imaging.

A phase III trial has been published in JACC  which concluded that it is a promising agent for detection of coronary artery disease in women, obese patients and patients undergoing pharmacological stress test [4]. A second phase III trial for Food and Drug Administration is ongoing (A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients with CAD; NCT01347710).

References

1. Berman DS et al. Improvement in PET myocardial perfusion image quality and quantification with flurpiridaz F 18. J Nucl Cardiol. 2012;19 Suppl 1:S38-45.
2. Yu M et al. The next generation of cardiac positron emission tomography imaging agents: discovery of flurpiridaz F-18 for detection of coronary disease. Semin Nucl Med. 2011;41:305-13.
3. Berman DS et al. Phase II safety and clinical comparison with single-photon emission computed tomography myocardial perfusion imaging for detection of coronary artery disease: flurpiridaz F 18 positron emission tomography. J Am Coll Cardiol. 2013;61:469-77.
4. Jamshid Maddahi, Joel Lazewatsky, James E Udelson, Daniel S Berman, Rob S B Beanlands, Gary V Heller, Timothy M Bateman, Juhani Knuuti, Cesare Orlandi. Phase-III Clinical Trial of Fluorine-18 Flurpiridaz Positron Emission Tomography for Evaluation of Coronary Artery Disease. J Am Coll Cardiol. 2020 Jul 28;76(4):391-401.