Flurpiridaz F 18 injection, a myocardial perfusion imaging (MPI) PET agent, appears to be safe and superior to SPECT with respect to image quality, diagnostic certainty and sensitivity for detection of coronary artery disease (CAD), according to a Phase II late-breaking clinical trial presented May 17 at the International Conference of Non-Invasive Cardiovascular Imaging (ICNC) in Amsterdam.
Jamshid Maddahi, MD, professor of nuclear medicine and cardiology at the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues enrolled 143 patients from 21 centers who underwent rest-stress PET and SPECT MPI. They used 99mTc-labeled tracer for all stress and 81 percent of rest SPECT MPI.
Of the 84 patients who underwent coronary angiography (mean age, 64.5 yrs; 68 males), 52 had significant CAD (at least 50 percent stenosis) by blinded quantitative analysis. The stress testing method was pharmacological coronary vasodilation in 45 of 84 patients and treadmill exercise in 39 of 84 patients. In each patient, three independent, blinded readers visually scored rest and stress images, determining a majority rule interpretation in each patient for both PET and SPECT.
According to the researchers, a significantly higher percentage of images were rated as either excellent or good on PET compared with SPECT stress images (99.2 vs. 88.8 percent) and rest images (96.8 vs. 64.8 percent). Also, diagnostic certainty of interpretation (percent of cases with definitely abnormal/normal interpretation) was significantly higher for PET compared with SPECT (92 vs. 76.8 percent).
Finally, the area under the ROC [receiver operating characteristic] curve for CAD diagnosis was significantly higher for PET versus SPECT (0.79 vs. 0.67). PET sensitivity was significantly higher than SPECT (78.8 vs. 61.5 percent). PET and SPECT specificities were not significantly different from one another (78.1 vs. 71.9 percent).
Maddahi and colleagues reported a total of 100 adverse events in 61/143 patients. Of these, seven (reported in two patients) were judged to be related to the study drug, but “none were serious,” the researchers said. Also, they said no clinical laboratory changes from baseline were reported as adverse events or considered as clinically significant. The ECG data at rest revealed no evidence of any clinically relevant effect on heart rate, PR interval, QRS duration or re-polarization.
“Results from this Phase II trial show that PET myocardial perfusion imaging with flurpiridaz F 18 demonstrate a strong safety profile and is superior to SPECT imaging with respect to the quality of rest and stress images, certainty of image interpretation, and diagnostic performance as measured by standard ROC analysis for detecting CAD,” said Maddahi.
In March, Lantheus Medical Imaging of North Billerica, Mass., received protocol assessment approval from the FDA for the Phase III trial of flurpiridaz F 18. The Phase III study will include two open-label, multicenter trials to assess the diagnostic efficacy (both sensitivity and specificity) of flurpiridaz F 18 PET MPI, compared with SPECT MPI in the detection of significant CAD.