Absolute quantitation of myocardial blood flow in human subjects with or without myocardial ischemia using dynamic flurpiridaz F 18 PET

Abstract

Absolute quantitation of myocardial blood flow (MBF) by PET is an established method of analyzing coronary artery disease (CAD) but subject to the various shortcomings of available radiotracers. Flurpiridaz F 18 is a novel PET radiotracer that exhibits properties of an ideal tracer.

Methods: A new absolute perfusion quantitation method with flurpiridaz was developed, taking advantage of the early kinetics and high first-pass extraction by the myocardium of this radiotracer, and the first-in-human measurements of MBF performed in 7 healthy subjects and 8 patients with documented CAD. PET images with time-activity curves were acquired at rest and during adenosine stress.

Results: In healthy subjects, regional MBF between coronary artery territories did not differ significantly, leading to a mean global MBF of 0.73 mL/min/g at rest and 2.53 mL/min/g during stress, with a mean global myocardial flow reserve (MFR) of 3.70. CAD vascular territories with <50% stenosis demonstrated a mean MBF of 0.73 at rest and 2.02 during stress, leading to a mean MFR of 2.97. CAD vascular territories with ≥50% stenosis exhibited a mean MBF of 0.86 at rest and 1.43 during stress, leading to a mean MFR of 1.86. Differences in stress MBF and MFR between normal and CAD territories, as well as between <50% and ≥50% stenosis vascular territories, were significant (P < 0.01).

Conclusion: Absolute quantitation of MBF in humans with the novel PET radiotracer flurpiridaz is feasible over a wide range of cardiac flow in the presence or absence of stress-inducible myocardial ischemia. The significant decrease in stress MBF and ensuing MFR in CAD territories allows a clear distinction between vascular territories exhibiting stress-inducible myocardial ischemia and those with normal perfusion.

Keywords: MBF; MFR; PET; flurpiridaz; human.

Figure 1

Polar maps in a CAD patient with stress images (A–C) and rest images (D–F) demonstrating a reversible defect affecting mostly the LAD territory. Early summed images (0.5–2 min) were re-oriented into short-axis views (A, D), polar maps generated (B, E), and normalized based on averages of normal subjects (C, F). The vascular territories and the left ventricular chamber were defined on the polar map automatically.

Figure 2

Left ventricular blood pool time-activity curve (TAC) (circle symbols) and Left Anterior Descending Artery TAC (lozenge symbols) obtained from predefined vascular ROI on the polar map during rest (A) and with adenosine stress (B) in a normal subject. The solid curve is the model fit to the vascular territory myocardial TAC based on a single-compartment model.

Figure 3

Regional MBF at rest (RMBF) and during adenosine stress (SMBF) and MFR in the 3 vascular territories of normal subjects.

Figure 4

Regional MBF at rest (RMBF) and during adenosine stress (SMBF) and MFR in vascular territories of normal subjects with low likelihood of myocardial ischemia vs. vascular territories of CAD patients with < 50% stenosis and ≥ 50% stenosis.

Figure 5

Scatterplot of the MFR obtained from each individual territory in normal subjects with low likelihood of myocardial ischemia vs. CAD patients with < 50% stenosis and ≥ 50% stenosis.