The role of cardiac PET imaging in cardiac amyloidosis.

Cardiac amyloidosis is an increasingly recognized infiltrative cardiomyopathy characterized by extracellular deposition of misfolded amyloid fibrils within the myocardium, leading to progressive heart failure, arrhythmias, and increased mortality. Although technetium-99m (Tc-99m) bone scintigraphy revolutionized the noninvasive diagnosis of transthyretin (ATTR) cardiac amyloidosis, important limitations remain, including limited quantification, reduced utility in immunoglobulin light-chain (AL) amyloidosis, and inability to comprehensively assess systemic disease burden or therapeutic response. Positron emission tomography (PET) has emerged as a promising next-generation molecular imaging modality capable of directly targeting amyloid fibrils and associated extracellular components. This review summarizes the evolving role of cardiac PET imaging in cardiac amyloidosis, including pathophysiologic principles, currently available and emerging radiotracers, clinical applications, diagnostic performance, and future directions. Amyloid-specific PET tracers such as 11C-PiB, 18F-florbetapir, 18F-florbetaben, and the novel pan-amyloid tracer 124I-evuzamitide demonstrate the ability to detect both ATTR and AL cardiac amyloidosis with high sensitivity while enabling quantitative assessment of amyloid burden. Emerging evidence suggests PET imaging may facilitate earlier disease detection, improve evaluation of equivocal conventional imaging findings, provide whole-body assessment of systemic amyloidosis, and allow longitudinal monitoring of treatment response in the era of disease-modifying therapies. Despite current limitations related to cost, availability, standardization, and regulatory approval, cardiac PET imaging is poised to become an increasingly important component of precision medicine approaches for systemic amyloid diseases. Continued advances in tracer development, quantitative imaging, and hybrid molecular imaging techniques are likely to further expand the role of PET in diagnosis, risk stratification, and therapeutic monitoring of cardiac amyloidosis.