Phase II Safety and Clinical Comparison With Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging for Detection of Coronary Artery Disease

Abstract

Objectives Phase II trial to assess flurpiridaz F 18 for safety and compare its diagnostic performance for PET myocardial perfusion imaging (MPI) to Tc-99m SPECT-MPI regarding image quality, interpretative certainty, defect magnitude and detection of coronary artery disease (CAD)(≥ 50% stenosis) on invasive coronary angiography (ICA). Background In preclinical and phase I studies, flurpiridaz F 18 has shown characteristics of an essentially ideal MPI tracer. Methods 143 patients from 21 centers underwent rest-stress PET and Tc-99m SPECT-MPI. Eighty-six patients underwent ICA, and 39 had low-likelihood of CAD. Images were scored by 3 independent, blinded readers. Results A higher % of images were rated as excellent/good on PET vs. SPECT on stress (99.2% vs. 88.5%, p<0.01) and rest (96.9% vs. 66.4, p<0.01) images. Diagnostic certainty of interpretation (% cases with definitely abnormal/normal interpretation) was higher for PET vs. SPECT (90.8% vs. 70.9%, p<0.01). In 86 patients who underwent ICA, sensitivity of PET was higher than SPECT [78.8% vs. 61.5%, respectively (p=0.02)]. Specificity was not significantly different (PET:76.5% vs. SPECT:73.5%). Receiver operating characteristic curve area was 0.82±0.05 for PET and 0.70±0.06 for SPECT (p=0.04). Normalcy rate was 89.7% with PET and 97.4% with SPECT (p=NS). In patients with CAD on ICA, the magnitude of reversible defects was greater with PET than SPECT (p=0.008). Extensive safety assessment revealed that flurpiridaz F 18 was safe in this cohort. Conclusions In this Phase 2 trial, PET MPI using flurpiridaz F 18 was safe and superior to SPECT MPI for image quality, interpretative certainty, and overall CAD diagnosis.

PET should not replace routine SPECT MPS for the assessment of patients with known or suspected CAD

“…In reality, this is not so because the distance traveled by the positron before annihilation is dependent on its energy and 82 Rb emits a particularly high energy positron. The positron range before annihilation is 8.6 mm for 82 Rb, 4.1 mm for 15 O, 2.5 mm for 13 N, and 1 mm for 18 F leading to spatial resolution greater than the 5-7 mm that is usually quoted for PET. 16 In practice the resolution of a 82 Rb image is no better than that of 99m Tc or 201 Tl images acquired using a solid-state camera (see Figure 1).…”

“…While accepting that PET MPS using 13 N-ammonia or 15 O-water provides better quality images and quantitative information compared with conventional SPECT, the need for an on-site cyclotron means that these agents are unlikely ever to be widely adopted. We, like others, are currently using 82 Rb PET in selected patients but its imaging characteristics are only slightly better, if at all, than SPECT especially if using a solidstate SPECT camera, and its cost-effectiveness is unproven.…”

“…15 Figure 1. MPS images from three different patients using thallium-201, technetium-99m-tetrofosmin, and rubidium-82.…”

PET myocardial perfusion quantification: anatomy of a spreading functional technique

“…A full 82 Rb 3D PET scan implies an exposure of ≈ 4.3 mSv, while for a single 13 N-ammonia 3D scan, the estimated the radiation dose is around 1, and 0.8 mSv for 15 O-H 2 O [9]. The calculated exposure for 18 F-flurpiridaz has initially been estimated in 6.3 mSv [7]. Notable, these doses are considerably lower than the ones for SPECT perfusion imaging.…”

“…Clinical protocols have been suggested for new promising compounds such as 18 F-flurpiridaz [7]. This fluorine-18-based tracer extends the possibilities of perfusion imaging implementation through a regional rather than on-site cyclotron due to its longer half-life (110 min).…”