Direct comparison uptake patterns of 99mTc-PYP and 99mTc-HMDP scintigraphy in cardiac amyloidosis with semi-quantitative analysis

Background Bone-avid tracers, such as 99m Tc-pyrophosphate (PYP) and 99m Tc-hydroxymethylene diphosphonate (HMDP), facilitate the noninvasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). In this study, we compared these two methods. Methods We retrospectively reviewed 83 patients with suspected or diagnosed cardiac amyloidosis (mean age, 79 years; 11 women) who underwent PYP and HMDP scintigraphy. Early (1 h) imaging was available for of 72/50 patients with PYP/HMDP, and all patients underwent delayed (3 h) imaging. Visual grading (Dorbala score), heart-to-contralateral lung (H/CL) ratios, and relative segmental uptake (RSU) derived from SPECT (3 h) polar map analysis using the quantitative perfusion SPECT software were compared. Results visual scores showed substantial agreement. The H/CL ratio showed a strong correlation. Bland–Altman analysis revealed fixed and proportional biases, with discrepancies increasing at higher uptake levels. The median H/CL values were comparable at 1 h, whereas HMDP showed slightly higher delayed values. Receiver operating characteristic analysis indicated excellent and good diagnostic accuracy at 1 and 3 h, respectively. Using routine diagnostic criteria, SPECT visual assessment demonstrated comparable diagnostic performance between PYP and HMDP. RSU analysis in 34 patients demonstrated similar segmental uptake distributions for both tracers, with basal and septal predominance, consistent with the apical-sparing patterns described previously. Conclusions PYP and HMDP demonstrated comparable diagnostic accuracies for ATTR-CA. PYP has been extensively validated and is suitable for early imaging, whereas HMDP has a slightly higher delayed uptake and lower blood pool activity. When interpreted using routine diagnostic criteria, SPECT provided equivalent diagnostic performance for PYP and HMDP. Segmental analyses confirmed the preservation of the characteristic apical sparing across the tracers. Both tracers are clinically interchangeable when standardized acquisition and interpretation protocols are applied.