Recent Progress in PET and SPECT Myocardial Perfusion Imaging: From Radiopharmaceuticals to Imaging Innovations

Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality worldwide, underscoring the need for accurate, noninvasive diagnostic methods to support clinical decision-making and treatment planning. Myocardial perfusion imaging (MPI) with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) plays a key role in the evaluation of myocardial ischemia and coronary artery disease. This review provides a comparative overview of PET and SPECT MPI, with particular emphasis on radiopharmaceuticals, technical advances, clinical applications, and the limitations of each modality.

A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for studies published between 1990 and July 2026. Search terms included myocardial perfusion imaging, PET radiotracers, SPECT radiotracers, rubidium-82, nitrogen-13 ammonia, technetium-99m sestamibi, flurpiridaz, and relevant combinations of these terms using Boolean operators. Original research articles, clinical trials, and review articles addressing radiopharmaceutical development, image reconstruction techniques, quantitative imaging, and hybrid PET/CT and SPECT/CT technologies were included. Non-English publications, case reports, and studies lacking relevant original or comparative data were excluded. The reference lists of eligible articles were also manually reviewed. Radiotracers were compared with respect to pharmacokinetics, myocardial extraction fraction, target-to-background ratio, image quality, radiation dosimetry, and clinical utility.

SPECT MPI, particularly with ⁹⁹mTc-sestamibi and ⁹⁹mTc-tetrofosmin, remains widely used because of its established clinical infrastructure, relatively low equipment costs, broad availability, and ability to assess both myocardial perfusion and left ventricular function using gated imaging. Its principal limitations include lower spatial resolution, susceptibility to photon attenuation artifacts, and a limited capacity for absolute quantification of myocardial blood flow. PET MPI offers superior spatial and temporal resolution, routine attenuation correction, and quantitative measurement of myocardial blood flow and myocardial flow reserve. Established PET tracers, including ⁸²Rb and ¹³N-ammonia, generally provide higher diagnostic accuracy than conventional SPECT; however, their short physical half-lives require generator-based or on-site cyclotron production and may limit the feasibility of exercise stress protocols. Emerging ¹⁸F-labeled tracers, particularly flurpiridaz, offer several advantages, including a longer half-life suitable for centralized production and distribution, improved image contrast, exercise stress imaging, rapid extracardiac clearance, and a more linear relationship between myocardial tracer uptake and blood flow over a broad flow range. Recent phase III studies have further supported the diagnostic performance of flurpiridaz.

PET and SPECT play important and complementary roles in noninvasive myocardial perfusion imaging. SPECT remains the most widely available and cost-effective technique, whereas PET provides superior image quality, attenuation correction, and quantitative assessment of myocardial blood flow. Ongoing advances in radiopharmaceutical development, hybrid imaging systems, reconstruction methods, and quantitative software are expected to further enhance the diagnostic and prognostic value of MPI and support increasingly personalized approaches to cardiovascular care.