Quantitative 99mTc-PYP SPECT/CT at 90 minutes improves diagnostic stratification in transthyretin cardiac amyloidosis

PURPOSE: Tc-labeled bone-seeking tracers is a cornerstone in the non-invasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). However, planar imaging alone, particularly in patients with Perugini score 1, often lacks diagnostic specificity. This study evaluates the incremental diagnostic value of quantitative SPECT/CT at 90 min post-injection (p.i.) when added to standard planar imaging at 60 and 180 min. METHODS: In this retrospective single-center study, 170 patients with suspected cardiac amyloidosis underwent 99mTc-PYP scintigraphy, including planar imaging and SPECT/CT. Quantitative myocardial uptake was assessed using myocardium-to-vertebra and myocardium-to-rib ratios across predefined left ventricular segments. Imaging findings were correlated with electrocardiographic, echocardiographic, cardiac magnetic resonance (CMR), biomarker, and histopathological data where available. RESULTS: Quantitative SPECT/CT correlated strongly with Perugini scores and improved diagnostic certainty, particularly in patients with equivocal planar findings. The addition of SPECT/CT led to diagnostic reclassification in more than one-third of patients, with the greatest impact observed in the intermediate Perugini group. Myocardial uptake ratios were significantly associated with NT-proBNP, troponin T, echocardiographic markers of diastolic dysfunction, and CMR parameters including native T1 and extracellular volume. Blood pool activity showed an inverse relationship with myocardial uptake and was associated with both upgrade and downgrade, indicating its role as a confounding factor. Correlation analysis demonstrated only weak associations with renal function and no meaningful correlations with biomarkers or structural parameters. Histopathology (7%) was concordant with imaging findings. CONCLUSION: Quantitative SPECT/CT at 90 min p.i. provides significant incremental diagnostic value, particularly in equivocal cases. Its ability to improve diagnostic classification and distinguish true myocardial uptake from blood pool activity supports its integration into routine diagnostic algorithms for ATTR-CM.