Design and Rationale of the REVEAL PET Study: A Study of 124I-evuzamitide to Diagnose Cardiac Amyloidosis.
| Title: | Design and Rationale of the REVEAL PET Study: A Study of 124I-evuzamitide to Diagnose Cardiac Amyloidosis. |
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| Authors: | Dorbala S; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA; Cardiac Amyloidosis Program, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: sdorbala@bwh.harvard.edu.; Maurer MS; Columbia University, New York, NY, USA.; Cuddy SAM; Cardiac Amyloidosis Program, Brigham and Women's Hospital, Boston, MA, USA.; Auer BD; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.; Kijewski MF; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.; Clerc OF; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.; Khouri MG; Duke University Health System, Durham, NC, USA.; Mitchell JD; Washington University, St. Louis, MO, USA.; Sperry BW; Mid America Heart Institute, Kansas City, MO, USA.; Hanna M; Cleveland Clinic, Cleveland OH, USA.; AbouEzzeddine OF; Mayo Clinic, Rochester, MN, USA.; Malhotra S; Cook County Health, Chicago, IL, USA.; Wall JS; University of Tennessee Graduate School of Medicine, Knoxville, TN, USA.; Guthrie S; Bayer AG, Clinical Development, Radiology, Berlin, Germany.; Di Carli MF; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.; Ruberg FL; Boston University, Boston Medical Center, Boston, MA, USA.; Dilsizian V; University of Maryland, Baltimore, MD, USA.; Dispenzieri A; Mayo Clinic, Rochester, MN, USA.; Udelson JE; Tufts Medical Center, Boston, MA, USA.; Narra RK; Medical College of Wisconsin, Milwaukee, WI, USA.; Masri AM; Oregon Health and Science University, Portland, OR, USA. |
| Source: | Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology [J Nucl Cardiol] 2026 Jun 15, pp. 102773. Date of Electronic Publication: 2026 Jun 15. |
| Publication Model: | Ahead of Print |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Inc. on behalf of American Society of Nuclear Cardiology Country of Publication: United States NLM ID: 9423534 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-6551 (Electronic) Linking ISSN: 10713581 NLM ISO Abbreviation: J Nucl Cardiol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2024- : New York : Elsevier Inc. on behalf of American Society of Nuclear Cardiology; Original Publication: St. Louis, MO : Mosby-Year Book, Inc., c1994- |
| Abstract: | Objective: To describe the rationale and design of the multicenter phase 3 Research with EVuzamitide to Evaluate for cardiac AmyLoidosis (REVEAL) trial evaluating the diagnostic performance of 124I-evuzamitide positron emission tomography/computed tomography (PET/CT) for detection of cardiac amyloidosis (CA) in patients undergoing evaluation for suspected disease.; Background: 124I-evuzamitide is a novel fibril-targeting positron emitting radiotracer that binds hypersulfated heparan sulfate glycans in amyloid fibrils across multiple amyloid subtypes.; Methods: This open-label, single-arm study, enrolled adults with suspected CA at 18 U.S.; Centers: Participants with previously diagnosed CA or systemic amyloidosis with known organ involvement, precursor protein targeted therapy use, estimated glomerular filtration rate < 15 mL/min/1.73 m2, recent myocardial infarction or recent heparin exposure were excluded. Cardiac and partial-body static PET/CT imaging was performed 4 ± 1 hours after intravenous administration of 124I-evuzamitide (1.0 ± 0.1 mCi). Potassium iodide was administered to reduce thyroid uptake of free radioiodine. Three blinded expert physicians independently assessed myocardial tracer uptake visually on PET/CT scans. Separately, three blinded amyloidosis experts adjudicated the presence or absence of CA, using standard-of-care clinical, laboratory, biopsy, genetic, electrocardiographic, echocardiographic, cardiac magnetic resonance, and bone-avid tracer cardiac scintigraphy data. The primary endpoints are sensitivity and specificity of visually interpreted 124I-evuzamitide PET/CT for diagnosis of CA compared with adjudicated standard-of- care diagnosis.; Conclusions: REVEAL is the first multicenter phase 3 study evaluating a fibril-targeted PET radiotracer for diagnosis of CA and may establish a non-invasive molecular imaging approach for detecting cardiac and systemic amyloid deposition across multiple amyloid subtypes.; (Copyright © 2026 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interestsSharmila Dorbala reports financial support was provided by Attralus, Inc. Sharmila Dorbala reports financial support was provided by Bayer AG. Sharmila Dorbala reports a relationship with Pfizer Inc that includes: consulting or advisory and funding grants. Sharmila Dorbala reports a relationship with Bridgebio Pharma Inc that includes: funding grants. Sharmila Dorbala reports a relationship with AstraZeneca Pharmaceuticals LP that includes: funding grants. Sharmila Dorbala reports a relationship with Medtrace that includes: consulting or advisory. Sharmila Dorbala reports a relationship with Ionis Pharmaceuticals Inc that includes: funding grants. Jonathan Wall has patent issued to Jonathan Wall. Abou Ezzeddine: Consulting income from Alnylam, BridgeBio, Medscape from WebMD, and Pfizer; and research funding from Pfizer Inc. Auer: Received travel reimbursement for speaking engagements from Spectrum Dynamics Medical, as well as in-kind research support from GE HealthCare. Clerc: Grant support from NIH K99HL175107, research grant from the American Society of Nuclear Cardiology and Pfizer Cuddy: Grant support from NIH 1K23HL166686-01 and AHA 23CDA857664; Institutional funding for Helios-B (Alnylam), Cardio-TTRansform (Ionis, Astra Zeneca), DepleTTR (Alexion), Magnitude (Intellia).; Personal consulting or speaker fees from Pfizer, Bayer, Intellia, Alnylam, AstraZeneca, Alexion and Novo-Nordisk, Attralus, Life molecular Imaging. Di Carli: Research grants: GE Healthcare, Sun Pharma, Gilead Sciences, Xylocor, Amgen. Consulting honoraria: GE Healthcare, MedTrace, Valo Health, Sofie, Bitterroot Bio Dilsizian: Consultant: GE Healthcare; CDL Nuclear Technologies Dispenzieri: Unpaid consulting: Alexion, CCO, Janssen, HemaLogiX Research: Pfizer, BMS, Takeda, Alexion, Abbvie; NIH CA186781 Dorbala: Research grants: NIH K24HL157648, R01HL159987, R01HL150342, Attralus, Astrazeneca, BridgeBio, GE Healthcare, Pfizer; Consultation: Medtrace. Guthrie: Employee of Bayer AG; Founder and Shareholder of Attralus Hanna: Advisory Boards for Pfizer, BridgeBio, Alnylam, AztraZeneca, Alexion, and Novo Nordisk Khouri: Has acted as a researcher for Alexion Pharmaceuticals, Alnylam Pharmaceuticals, AstraZeneca, Attralus, BridgeBio Pharma, Intellia Therapeutics, Ionis Pharmaceuticals, and Pfizer; and as a consultant, advisor, or speaker for Alnylam Pharmaceuticals, AstraZeneca, BridgeBio Pharma, and Pfizer. Kijewski: None. Malhotra: Speakers Bureau - Pfizer, Alnylam, BridgeBio and AstraZeneca. ; Consultant - Pfizer, Alnylam, BridgeBio and AstraZeneca Mangal: Employee of Solara Consulting Corp. BC, Canada Masri: Research grants from Pfizer, Attralus, Cytokinetics and Janssen. Personal consulting fees from Cytokinetics, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Edgewise, Rocket, Lexeo, Prothena, BioMarin, AstraZeneca, Avidity, and Neurimmune. Maurer: Grant support from NIH R01HL177670, R01AG093132 and R01AG081582; grants and personal fees from Alnylam, Pfizer, BridgeBio, Intellia and Ionis; and personal fees from AstraZeneca and Bayer. Mitchell: Research support from Abbott Laboratories and Myocardial Solutions. Consulting fees from Alnylam, AstraZeneca, BridgeBio and Pfizer. Narra: Consulting or speaker fees: Sanofi, AstraZeneca, Incyte Ruberg: Research grants: NIH R01HL177670 and R01AG093132, AstraZeneca/TriNetX, Anumana, BridgeBio, Pfizer. Consulting: eMyosound, Attralus Sperry: Consulting Fees from Alnylam, AstraZeneca, BridgeBio, Pfizer, SpectrumDynamics. Udelson: Research grants: Attralus, Medtrace Wall: unding from the NIH; Founder, shareholder, and CSO of Attralus, Inc; Intellectual property rights related to amyloid binding peptides and antibodies; Consultant for Bayer AG. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paperIf there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: (124)I-evuzamitide; Cardiac amyloidosis; Diagnosis; PET/CT; Phase 3 study; Systemic amyloidosis |
| Entry Date(s): | Date Created: 20260615 Latest Revision: 20260615 |
| Update Code: | 20260616 |
| DOI: | 10.1016/j.nuclcard.2026.102773 |
| PMID: | 42297126 |
| Database: | MEDLINE |
Journal Article