Progress in the Application of Positron Emission Tomography Amyloid Radiotracers in Cardiac Amyloidosis

Cardiac amyloidosis (CA) is a progressive and life-threatening manifestation of systemic amyloidosis characterized by extracellular deposition of insoluble amyloid fibrils in the myocardium. The two most common subtypes of CA are immunoglobulin light-chain (AL) and transthyretin (ATTR) amyloidosis, with ATTR further classified into hereditary (ATTRv) and wild-type (ATTRwt) forms. Early and accurate diagnosis of CA remains challenging, as the current gold standard, endomyocardial biopsy, is invasive and subject to sampling heterogeneity. In recent years, the rapid development of positron emission tomography (PET) molecular imaging has offered new possibilities for noninvasive detection, quantification, and monitoring of cardiac amyloid deposition. This review summarizes recent advances in PET imaging applied to CA, focusing on the performance and clinical potential of several emerging amyloid-targeting radiotracers. 11C-PiB demonstrates excellent sensitivity for detecting AL-CA but is limited by its short half-life (20 minutes) and high production costs. 18F-florbetapir, with a longer half-life of approximately 2 hours, shows promise for identifying CA and monitoring disease progression, although its ability to distinguish AL from ATTR subtypes remains suboptimal. Similarly, 18F-florbetaben and 18F-flutemetamol have been employed for cardiac amyloid imaging, with encouraging results in detecting myocardial amyloid burden, yet their specificity for amyloid subtyping requires further validation. The novel radiotracer 124I-evuzamitide (124I-p5+14) has demonstrated broad-spectrum targeting of systemic amyloid deposits and superior performance in imaging multiorgan involvement, although its prolonged half-life and associated radiation exposure may limit widespread clinical use. Future directions include the development of subtype-specific PET tracers, optimization of quantitative imaging techniques, and the integration of artificial intelligence for automated burden assessment and prognostication. Furthermore, PET imaging has the potential to serve as a biomarker for treatment response, facilitating individualized therapeutic strategies. Advances in amyloid PET imaging will undoubtedly play a crucial role in improving the diagnosis, management, and long-term prognosis of patients with cardiac amyloidosis.