Cardiac PET: Quantitating myocardial blood flow with F-18 flurpiridaz
The quantitative imaging of myocardial blood flow (MBF) has been gaining momentum in recent years, as is the use of F-18 flurpiridaz, which has been shown to reveal a clear demarcation of disease in patients with CAD, according to a first-in-human quantitative imaging study published July 28 in the Journal of Nuclear Medicine.
Rene R.S. Packard, MD, from the department of medicine, cardiology, at the University of California, Los Angeles, and colleagues documented the absolute quantitation of MBF using PET and the investigational tracer F-18 flurpiridaz, which was found to have early kinetics and high extraction in myocardium by the first pass and a few important advantages over more mainstream tracers.
“PET radiotracers such as Rb-82 chloride, N-13 ammonia, and O-15 water have been used to quantitate absolute MBF,” wrote Packard et al. “Because of their short half-lives, O-15 is limited to facilities with an on-site cyclotron, and N-13 requires either an on-site or a nearby cyclotron. Rb-82 is generator-produced and is approved for the clinical assessment of myocardial perfusion. However, its short half-life affects image quality with noisy time–activity curves, reducing the tracer’s ability to quantify myocardial perfusion.”
Flurpiridaz exhibits rapid uptake and longer washout in cardiomyocytes, making it an attractive tracer for this application. The compound is partly an analog of the insecticide pyridaben, an inhibitor of the mitochondrial complex-1 of the electron transport chain. It is an ideal tracer because while it shows strong binding to cardiomyocytes, it does not hamper their function. Previous studies showed that PET imaging with the tracer provided strong and steady cardiac uptake on the level of blood flow.
For this study, absolute quantitation of MBF were noted for eight patients with CAD and seven healthy controls. PET imaging was performed and time-activity curves were documented at rest and via adenosine stress. Results showed no substantial differences in regional MBF in the coronary arteries of healthy subjects, but a significant change in those with varying degrees of stenosis. The mean global MBF was 0.73 mL/min/g at rest and 2.53 during stress. The mean global myocardial flow reserve (MFR) ended up being 3.70. Subjects with CAD and less than 50 percent stenosis showed a mean MBF of 0.73 at rest and, during stress, 2.02. The mean MFR was 2.97. Those who displayed CAD with equal to or greater than 50 percent stenosis were found to have a mean MBF of 0.86 at rest and 1.43 during stress and a mean MFR of 1.86.
“In CAD patients, diseased vascular segments had significantly lower MBF in response to adenosine stress and thus a reduced MFR,” the authors concluded. “Future studies will determine cutoff values for stress MBF and MFR in patients with CAD for direct clinical applicability. We believe patient risk stratification using PET imaging will be feasible in a broad clinical setting using both relative perfusion and the absolute quantitation of MBF. These initial results suggest that flurpiridaz, which is not yet approved by the U.S. Food and Drug Administration as a PET MPI agent, is uniquely poised as a radiotracer to fulfill all these requirements.”