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Clinical Trial
. 2025 Jul;18(7):799-811.
doi: 10.1016/j.jcmg.2025.01.018. Epub 2025 May 28.

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

Dia A Smiley  1 , Andrew J Einstein  2 , Kevin J O'Gorman  3 , Denisse Santana  1 , Sergio Teruya  1 , Nicholas Chan  1 , Ani Nalbandian  1 , Timothy J Poterucha  1 , Stephen T Helmke  1 , Akiva Mintz  4 , Kim Goldner  4 , Miroslav Sekulic  5 , Alfonsina Mirabal  1 , Margaret O Cuomo  1 , Samantha Guadalupe  1 , Jeffeny De Los Santos  1 , Mary E Paulino  1 , Kimberly A Mateo  1 , Carlos M Rodriguez  1 , Massiel Jimenez  1 , Abdirahman Wardhere  1 , Dimitrios Bampatsias  1 , Michelle Castillo  1 , Boyu Peng  4 , Mathew S Maurer  6
Affiliations
Clinical Trial

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

Dia A Smiley et al. JACC Cardiovasc Imaging. 2025 Jul.

Abstract

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).

Keywords: (124)I-evuzamitide; PET/CT; PYP; cardiac amyloidosis; transthyretin; variant.

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Conflict of interest statement

Funding Support and Author Disclosures This study was funded by Attralus. Dr Smiley has received salary support from the Amyloidosis Foundation and the American Society of Nuclear Cardiology/Pfizer Young Investigator Award. Dr Einstein has received authorship royalties from Wolters Kluwer Healthcare–UpToDate; has served as a consultant to Artrya; has served on a scientific advisory board for Canon Medical Systems USA; and has received research grants to Columbia University from BridgeBio, Canon Medical Systems USA, GE HealthCare, Ionis, Intellia, Mediwhale, Neovasc, Pfizer, Roche Medical Systems, and W.L. Gore and Associates. Dr O’Gorman is an active-duty service member in the U.S. Air Force (the views expressed by the authors do not reflect the official policy or position of the Defense Health Agency, the U.S. Department of Defense, or any agencies of the U.S. government); owns stock (<$5,000 in each) in Abbott Laboratories, Boston Scientific, Intuitive Surgical, Eli Lilly, Thermo Fisher Scientific, Viking Therapeutics, UnitedHealth Group, and Danaher. Dr Chan has received funding and salary support from the Amyloidosis Foundation. Dr Mintz has received consulting payments from Novartis and is the principal investigator of a research grant sponsored by Alexion. Dr Poterucha owns stock in Abbott Laboratories and Baxter International; and has received research support provided to his institution from the Amyloidosis Foundation, the American Heart Association, BridgeBio, Janssen, Pfizer, and Edwards Lifesciences. Dr Bampatsias has been supported by the Cardiac ATTR Amyloidosis Fellowship grant funded by the International Society of Amyloidosis. Dr Maurer has received grant support from the National Institutes of Health (R01HL139671 and AG081582); has received grants from Alnylam, BridgeBio, Intellia, and Ionis; and has received personal fees from Alnylam, Novo Nordisk, Roche, Prothena, AstraZeneca, Akcea, and Intellia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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