Quantifying Myocardial Blood Flow: An Expanding Role for PET?

The possibility of quantifying myocardial blood flow (MBF) with PET imaging has existed for decades, but its clinical use has been limited. MBF is assessed more often in relative terms, with visible differences in flow between regions of myocardium, used as an indicator of problems. Now, new developments in tracers could make cardiac PET the more precise approach for absolute quantification.

PET, with its high image quality and robust attenuation algorithm, can measure MBF in absolute terms, thus avoiding the problems of relative assessment experienced with SPECT. Kajander et al studied the benefit of absolute quantification using PET over relative assessment using conventional angiography. They found that absolute quantification had a positive predictive value, negative predictive value and accuracy of detecting obstructive CAD of 86 percent, 97 percent and 92 percent, respectively (Circ Cardiovasc Imaging 2011;6:678-684). This is compared with values of 61 percent, 83 percent and 73 percent, respectively, for relative assessment.

However, the application of absolute MBF quantification by PET has been limited clinically. Part of this is due to limitations of PET tracers, as well as the restricted availability of PET cameras for cardiac studies conducted in academic centers.

Searching for the perfect tracer

Absolute blood flow measurements have been conducted with Rb-82, N-13 ammonia and O-15 water tracers, though each has its own set of drawbacks:

• O-15 water: Typically, this tracer is used only in research as it is not FDA approved and not reimbursed by the Centers for Medicare & Medicaid Services (CMS). It requires an onsite cyclotron, a cost most facilities would like to avoid, and with a two-minute half-life, unit dose orders are impractical. Also, the myocardium cannot be visualized with O-15 water.
• N-13 ammonia: This tracer is both FDA approved and reimbursed by CMS. Like O-15 water, though, N-13 ammonia is cyclotron produced with a half-life of 10 minutes, which restricts its use to clinics equipped with cyclotrons.
• Rb-82: Rubidium tracers have only a 72 second half-life, but are produced by a column generator, not a cyclotron. While there are high costs for a generator—approximately $30,000 for a month's use—it is still more accessible than a cyclotron.

While the current crop of tracers is held back by costly equipment, a new F-18-based flow agent could shake up the nuclear cardiology space, says Georges El Fakhri, PhD, of the department of radiology at Massachusetts General Hospital in Boston. F-18 labeled flow agents, such as flurpiridaz, have a half-life of 110 minutes, which means a dose order could be manufactured and shipped rather than having to be produced onsite. While still undergoing clinical trials, preliminary results are spreading optimism about its potential future clinical use.

The results have demonstrated that the extraction fraction of F-18 perfusion "is much better than that of ammonia," and if F-18 flow agents get FDA clearance, El Fakhri predicts it "could have a major impact on cardiac PET imaging."

Studies, such as one by Sherif et al, have shown the usefulness of F-18 flurpiridaz in quantifying blood flow, and demonstrated favorable results when compared with other PET and SPECT agents. High extraction of a tracer improves reliability of flow quantification and F-18 flurpiridaz was shown to have an extraction fraction of 0.94. This is compared with extraction fractions of 0.38 for 99mTc-sestamibi, and 0.42 for Rb-82 (J Nucl Med 2011;52:617-624).  

"The agents that are used currently still have some limitations in terms of their pharmacokinetic properties as blood flow tracers, so a better scanner is not going to help you overcome those limitations," says Gary D. Hutchins, PhD, of the department of radiology at the Indiana University School of Medicine in Indianapolis.

"Regulatory agencies ultimately will drive the future of MBF quantification," he says. PET is used very heavily in oncology, where it is FDA approved and nets CMS reimbursement, and even if the number of PET scanners expands, adoption will come only with regulatory approval.

The success of PET in oncology could facilitate its use in cardiology, says Vasken Dilsizian, MD, chief of the division of nuclear medicine at the University of Maryland Medical Center in Baltimore. The superior resolution of PET allows it to detect tumors mere millimeters in size, and most PET labs across the U.S. have been dedicated to oncology, with cardiac PET competing for utilization. As the number of PET scanners increases for use in cancer studies, however, there may be more opportunities for cardiac PET procedures.

"There is no doubt that PET will steadily and slowly replace SPECT systems in the coming years because of its technological advancement and extremely high quality images," says Dilsizian.