Uncertain Clinical Relevance of Serial Bone Scintigraphy Findings in Treated Transthyretin Amyloid Cardiomyopathy

Available online 9 July 2025

Author links open overlay panel, , , , , , , , , , , , , , , , , , , …AbstractBackground

Technetium-99m–labeled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy is a critical part of the validated nonbiopsy diagnostic algorithm for transthyretin amyloid cardiomyopathy (ATTR-CM). With the advent of novel disease-modifying therapies for ATTR-CM, there is intense interest in establishing the utility of DPD scans as an indicator of treatment response.

Objectives

The authors conducted a retrospective multimodality imaging study to determine the utility of 99mTc-DPD to track treatment response in ATTR-CM.

Methods

ATTR-CM patients from the United Kingdom National Amyloidosis Centre who were receiving amyloid-specific disease-modifying therapy (DMT) and underwent pre- and post-treatment 99mTc-DPD/single-photon emission computed tomography–computed tomography scans were included. Myocardial percentage injected dose (PID), a proposed scintigraphic indicator of cardiac amyloid burden, was measured at baseline and follow-up. Change from baseline in this variable was compared with that of other validated biomarkers of disease severity.

Results

A total of 66 patients with ATTR-CM who received DMT underwent serial 99mTc-DPD scans. At follow-up, with a median time between 99mTc-DPD scans of 27.5 months (Q1-Q3: 21.9-33.1 months), there was a mean reduction from pre-DMT myocardial PID on 99mTc-DPD scintigraphy of 1.5 ± 1.5%. No statistically significant correlation between the change in PID at follow-up and change in echocardiographic, biochemical, or cardiac magnetic resonance parameters was identified. Discordance in which there was an improvement on follow-up 99mTc-DPD scintigraphy despite disease progression was observed in 28/66 patients (42.4%).

Conclusions

Our study indicates a poor correlation between reduction in 99mTc-DPD uptake at follow-up and numerous established biomarkers of ATTR-CM treatment response. Changes in DPD uptake in ATTR-CM patients receiving DMT should be interpreted with caution.

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