PET and SPECT Tracers for Myocardial Perfusion Imaging

Coronary artery disease has been the leading cause of death since the 1960s, which has motivated the research and development of myocardial perfusion imaging (MPI) agents for early diagnosis and to guide treatment. MPI with SPECT has been the clinical workhorse for MPI, but over the past two decades PET MPI is experiencing growth due to enhanced image quality that results in superior diagnostic accuracy over SPECT. Furthermore, dynamic PET imaging of the tracer distribution process from time of tracer administration to tracer accumulation in the myocardium has enabled routine quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) in absolute units. MBF and MFR incrementally improve diagnostic and prognostic accuracy over MPI alone. In some cases (eg, rubidium PET imaging with pharmacologic stress) MPI, MBF, and MFR can be acquired simultaneously without incremental cost, radiation exposure, or significant processing time. Nuclear cardiology clinics have been looking to incorporate MBF quantification into clinical routine, but traditional SPECT and MPI tracers are inadequate for this challenge. Cardiac dedicated SPECT scanners can also perform dynamic imaging and have stimulated research into MBF quantification using SPECT tracers. New perfusion tracers must be tailored for emerging clinical needs (including MBF quantification), technical capabilities of imaging instrumentation, market constraints, and supply chain feasibility. Because these conditions have been evolving, tracers previously considered inferior may be reconsidered for future applications and some recently developed tracers may be suboptimal. This article reviews current, clinically-available tracers and those under development showing greatest potential. It discusses for each tracer the rationale for development, physiological mechanism of uptake by the myocardium, published evaluation results and development state. Finally, it gauges the suitability of each tracer for clinical application. The article demonstrates an acceleration in the pace of perfusion radiotracer development due to better understanding of the relevant physiology, better chemistry tools and small animal imaging. Consequently, bad tracers may fail faster and with less wasted investment, and good tracers may translate more efficiently from bench to bedside.