Cardiac PET Perfusion Tracers: Current Status and Future Directions

Abstract

Positron emission tomography (PET) myocardial perfusion imaging (MPI) is increasingly used for non-invasive detection and evaluation of coronary artery disease (CAD). However, the widespread use of PET MPI has been limited by shortcomings of the current PET perfusion tracers. Availability of these tracers is limited by need for an on-site (15O water and 13N ammonia) or nearby (13N ammonia) cyclotron or commitment to costly generators (82Rb). Due to short half-lives ranging from 76sec for 82Rb, to 2.1min for 15O water and 10min for 13N ammonia, their use in conjunction with treadmill exercise stress testing is either not possible (82Rb and 15O water) or is not practical (13N ammonia). Furthermore, the long positron range of 82Rb makes image resolution suboptimal and its low extraction limits its defect resolution. In recent years, development of an 18F labeled PET perfusion tracer has gathered considerable interest. The longer half-life of 18F (108 minutes) would make the tracer available as a unit dose from regional cyclotrons and allow use in conjunction with treadmill exercise testing. Furthermore, the short positron range of 18F would result in better image resolution. 18F flurpiridaz is by far the most thoroughly studied in animal models, and is the only F18-based PET MPI radiotracer currently undergoing clinical evaluation. Pre-clinical and clinical experience with 18F flurpiridaz demonstrated a high myocardial extraction fraction, high image and defect resolution, high myocardial uptake, slow myocardial clearance, and high myocardial-to-background contrast which was stable over time – important properties of an ideal PET MPI radiotracer. Pre-clinical data from other 18F labeled myocardial perfusion tracers are encouraging.

Validation of pixel-wise parametric mapping of myocardial blood flow with 13NH3 PET in patients with hypertrophic cardiomyopathy

“…The ability of 13 NH 3 to provide separate subendocardial and subepicardial MBF values allowing transmural MBF analysis could have important clinical consequences given the importance of expanding the role of PET measurements and the various advantages that 13 NH 3 has in clinical practice [2][3][4]. Of the other available tracers, 82 Rb would probably have major limitations in spatial resolution for transmural measurements because of the relatively long distance covered by its high-energy positrons [33]. Because it is labelled with 18 F, flurpiridaz could possibly be more promising for this purpose, although the definition and validation of convincing models for MBF quantitation are still to be completed [34].…”

A New Era of Myocardial Perfusion Imaging

“…Furthermore, higher myocardial extraction facilitates detection of milder perfusion defects Higuchi et al 18 makes it an optimal candidate for absolute MBF quantitation (5). In a rat biodistribution study, heart-to-lung and heart-toliver ratios of 18 F-Flurpiridaz were significantly higher than that of 99m Tc-sestamibi SPECT (17).…”

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

“…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).…”