Early Detection of Transthyretin Cardiac Amyloidosis Using 124I-Evuzamitide Positron Emission Tomography/Computed Tomography.

BACKGROUND

Early detection of transthyretin cardiac amyloidosis (ATTR-CA) is vital, because currently available therapies are most effective early in the disease course. Although Perugini grade 2 or 3 uptake on scintigraphy using bone-avid tracers such as 99mTc-pyrophosphate is highly specific for ATTR-CA, absent monoclonal proteins, sensitivity is about 70%. Positron emission tomographic (PET)/computed tomographic (CT) imaging using the novel radiolabeled heparan sulfate proteoglycan-binding peptide 124I-evuzamitide has been shown to be useful for quantifying cardiac amyloid load in systemic amyloidosis.

OBJECTIVES

The aim of this study was to quantify myocardial 124I-evuzamitide PET uptake and compare diagnostic performance with that of 99mTc-pyrophosphate in patients with ATTR-CA and carriers.

METHODS

Twenty-five subjects underwent imaging using 124I-evuzamitide PET/CT imaging: 7 with wild-type ATTR-CA (all Columbia stage I) and 18 transthyretin amyloidosis (ATTR) variant-allele carriers with cardiomyopathy and/or neuropathy. Myocardial uptake was determined as left ventricular percentage of injected dose (mean activity concentration × volume/injected activity) and cardiac amyloid activity (mean specific uptake value × volume) within voxels with uptake above blood pool.

RESULTS

Eleven subjects with ATTR and Perugini grade 0 or 1 99mTc-pyrophosphate cardiac scans had cardiac uptake of 124I-evuzamitide, suggesting that 124I-evuzamitide PET/CT imaging may detect ATTR amyloid deposits when 99mTc-pyrophosphate cardiac scintigraphy does not. 124I-evuzamitide showed myocardial uptake in all 5 subjects with variant ATTR with biopsy-proven disease and in 2 subjects with wild-type ATTR and negative (grade 0) results on 99mTc-pyrophosphate scans but extracardiac biopsies showing ATTR. Myocardial amyloid load was moderately to strongly correlated with disease stage and with echocardiographic and quality-of-life measures.

CONCLUSIONS

124I-evuzamitide PET/CT imaging can identify myocardial amyloid in variant transthyretin allele carriers and wild-type subjects when 99mTc-pyrophosphate does not. (Evuzamitide in PET/CT to Measure Potential Therapeutic Response in ATTR; NCT05635045).