Kinetics of Technetium-Labeled Cardiac Amyloid Radionuclide Imaging

BACKGROUND: Technetium-labeled bone-avid tracers have been repurposed to diagnose transthyretin cardiac amyloidosis without rigorous kinetic studies. Supply shortages have necessitated the use of hydroxymethylene diphosphonate (HMDP) as an alternative to technetium-99m pyrophosphate, though comparative data remain limited. This study characterizes tracer kinetics using quantitative single-photon emission computed tomography with computed tomography. METHODS: Twenty-four subjects undergoing evaluation for transthyretin cardiac amyloidosis underwent serial single-photon emission computed tomography with computed tomography imaging with pyrophosphate (n=11) or HMDP (n=13) on a cadmium zinc telluride system (SpectrumDynamics Veriton). Single-photon emission computed tomography acquisitions were obtained at intervals from 5 minutes to 3 hours post-injection. Quantitative parameters included standardized uptake values (SUVs), target-to-background ratios, and total cardiac activity derived from 3-dimensional volumes of interest for myocardium, blood pool, and bone. Mixed-effects models with splines compared time-activity trends between tracers. RESULTS: All 16 subjects with positive imaging demonstrated visual myocardial uptake above the blood pool within 10 minutes post-injection. Myocardial SUVs were similar between tracers and decreased linearly over time, whereas blood pool SUVs declined biexponentially and bone SUVs increased exponentially. HMDP exhibited faster blood pool clearance and higher bone uptake than pyrophosphate, resulting in higher heart-to-blood pool target-to-background ratios across all time points. Bone activity exceeded myocardial activity earlier with HMDP (mean ≈90 versus 130 minutes; P <0.001), resulting in a visual reduction of myocardial intensity with HMDP due to scaling. No association was observed between quantitative indices and clinical disease severity markers. CONCLUSIONS: Both pyrophosphate and HMDP provide diagnostic myocardial visualization within 10 minutes of injection, with similar myocardial SUVs that decline linearly over time. HMDP demonstrates more rapid blood pool clearance and greater bone uptake, resulting in earlier skeletal dominance and often requiring upward adjustment of image intensity to visualize myocardial uptake on delayed images. The results provide kinetic data that can inform future protocol optimization and quantitative standardization.