The Second Phase-3 Multi-Center Trial of Flurpiridaz F-18 PET Myocardial Perfusion Imaging for Coronary Artery Disease Evaluation

Introduction: Flurpiridaz F-18 (flurpiridaz) is a novel PET myocardial perfusion imaging tracer with outstanding imaging characteristics. The aim of this study was to further assess the diagnostic efficacy and safety of flurpiridaz PET for the detection and evaluation of coronary artery disease (CAD) defined as >50% stenosis by quantitative invasive coronary angiography (ICA) in a multi-center prospective international clinical trial. The primary end point was to assess the diagnostic efficacy (sensitivity and specificity) of flurpiridaz PET MPI for the detection of significant CAD. The secondary end points were to compare the diagnostic performance of flurpiridaz PET MPI vs. Tc-99m SPECT MPI in the detection of CAD in all patients (key secondary endpoint) and in the clinically important subgroups of women, patients with body mass index (BMI) ≥30 kg/m², and those with diabetes. In addition, PET MPI and Tc-99m SPECT MPI were compared for defect severity/extent, image quality, confidence of interpretation and radiation dose to patients. The safety of flurpiridaz PET MPI was also evaluated.

Methods: 730 patients with suspected CAD from 48 clinical sites in US, Canada and Europe were enrolled. Patients underwent 1-day rest/stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m labeled SPECT before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. ICA was quantified by a core laboratory expert who was blinded to clinical and image data.

Results: 578 patients (age, 63.7+9.5 years) were evaluable. 32.5% were women, 52.3% had BMI≥30, and 33.6% had diabetes. Flurpiridaz PET met the prespecified primary endpoint of the study; sensitivity and specificity were significantly higher than the prespecified threshold value by two of the three readers. Analysis of the secondary endpoints showed that flurpiridaz PET sensitivity and specificity met the predefined criterion of being significantly higher than SPECT by two of the three readers in the overall population as well as in women, in patients with BMI ≥30 kg/m², and in diabetic patients. By majority rule analysis, sensitivity and specificity of flurpiridaz PET were 80.3% and 63.8% that were significantly higher (p<0.0004) than those of SPECT 63.8% and 61.7% respectively. Furthermore, flurpiridaz PET ROC area under the curves were significantly higher than SPECT in the overall population (0.80 vs 0.68, p<0.0001), in women (0.84 vs 0.70, p<0.01), and in patients with BMI ≥30 kg/m² (0.79 vs 0.67, p<0.001). In diabetic patients, ROC area under the curves were not significantly different between flurpiridaz PET and SPECT (0.76 vs 0.69, p=0.088). Flurpiridaz PET was also superior to SPECT for assessment of defect extent/severity (p<0.0001). Image quality (% excellent or good) of flurpiridaz PET was significantly better than SPECT for rest images (93% vs 72%, p<0.0001), pharmacological stress images (96% vs 78%, p<0.0001), and treadmill exercise images (97% vs 87%, p<0.05). Radiation exposure, evaluated in 604 dosed patients, was less for PET (including 0.64 mSv radiation dose from CT based attenuation correction) than same-day rest/stress SPECT using either Tetrofosmin or Sestamibi with a mean total decay-corrected effective dose (rest+ stress) of 6.25 mSv for flurpiridaz PET, 9.86 mSv for 99mTc-tetrofosmin SPECT and 12.41 mSv for 99mTc-sestamibi SPECT.

Conclusions: This second flurpiridaz PET myocardial perfusion imaging multicenter international trial demonstrates that flurpiridaz has promise as a new tracer for detection and evaluation of coronary artery disease. This is particularly so in women and patients with BMI ≥30 kg/m².