Multicentre study of activity quantification methods for 99m-Tc-pyrophosphate SPECT/CT in cardiac amyloidosis

Objective 99mTc-PYP SPECT/CT imaging is used for diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). The calculation of quantitative metrics allows assessment of the myocardial amyloid burden and supports therapy response evaluations. This study explores the implementation of reliable metrics and the validation of activity quantification methods in a multicentre study. Methods: As part of the IAEA Transthyretin Amyloid Cardiomyopathy (iTAC) project, a multicentre phantom study was conducted at 10 institutions using 12 hybrid SPECT/CT systems. Standardized acquisitions consistent with clinical protocols were used to compute the activity calibration factors (ACF). Absolute activity verifications were based on cardiac insert measurements with known activity distributions. Multiple reconstruction/quantification approaches (RecMethod) were evaluated, including the institution method (SiteProc) and four alternative ones; results of the computed activity were compared with the true activity meter measurements. Accuracy was assessed using RecMethod-to-True activity ratios, summarized by median, interquartile range (IQR) and coefficient of variation (CV). Results: Most institution ACF values (ACF SiteProc ) ranged 75–105 cps/MBq and were consistent with reference CoreLab estimates. Agreement between ACF SiteProc and reference CoreLab values showed a median ratio of 99.6 %, IQR 5.8 %, and CV 9.4 %, indicating no systematic bias. For activity quantification, median RecMethod-to-True ratios were 100.1 % for the SiteProc reconstructions and 97.8 %, 94.1 %, 95.6 % and 96.0 % for the alternatives. Conclusion: The evaluated quantification methods demonstrated good median accuracy across institutions providing reliable activity estimates, essential for a robust implementation of quantitative metrics for ATTR-CA. The obtained inter-site variability indicates that precision remains a challenge at the multicentre quantitative imaging studies.