2. Academic Validation
  3. Cardiac Amyloid Quantification Using 124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir: A Pilot PET/CT Study

Cardiac Amyloid Quantification Using 124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir: A Pilot PET/CT Study

  • JACC Cardiovasc Imaging. 2023 Nov;16(11):1419-1432. doi: 10.1016/j.jcmg.2023.07.007.
Olivier F Clerc 1,  Sarah A M Cuddy 2,  Matthew Robertson 3,  Shilpa Vijayakumar 2,  Jocelyn Canseco Neri 1,  Vaidehi Chemburkar 1,  Marie Foley Kijewski 4,  Marcelo F Di Carli 5,  Giada Bianchi 6,  Rodney H Falk 7,  Sharmila Dorbala 8
Affiliations

Affiliations

  • 1 Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 2 Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; CV imaging program, Cardiovascular Division and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • 3 CV imaging program, Cardiovascular Division and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • 4 Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 5 Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; CV imaging program, Cardiovascular Division and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • 6 Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Division of Hematology, Department of Medicine, Brigham and Women's Hospital Boston, Massachusetts, USA.
  • 7 Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 8 Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Cardiac Amyloidosis Program, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; CV imaging program, Cardiovascular Division and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address: sdorbala@bwh.harvard.edu.
PMID: 37676210 DOI: 10.1016/j.jcmg.2023.07.007
Abstract

Background: Cardiac amyloid quantification could advance early diagnosis of amyloid cardiomyopathy (CMP) and treatment monitoring. However, current imaging tools are based on indirect measurements. 124I-evuzamitide is a novel pan-amyloid radiotracer binding to amyloid deposits from multiple amyloidogenic proteins. Its ability to quantify cardiac amyloid has not yet been investigated.

Objectives: The objectives of this pilot study were to quantify myocardial 124I-evuzamitide uptake and to compare its diagnostic value to 18F-florbetapir in participants with amyloid CMP and control subjects.

Methods: This study included 46 participants: 12 with light-chain (AL) CMP, 12 with wild-type transthyretin (ATTRwt) CMP, 2 with hereditary amyloidosis, and 20 control subjects. All amyloidosis participants underwent positron emission tomography/computed tomography with 124I-evuzamitide and 18F-florbetapir. Control subjects underwent 124I-evuzamitide (n = 10) or 18F-florbetapir (n = 8) positron emission tomography/computed tomography. Left ventricular percent injected dose (LV% ID) was measured as mean activity concentration × myocardial volume/injected activity. High LV %ID was defined using Youden's index.

Results: In CMP participants, median age was 74 years and 92% were men. 124I-evuzamitide LV %ID differed across groups: median AL-CMP 1.48 (IQR: 1.12-1.89), ATTRwt-CMP 2.12 (IQR: 1.66-2.47), and control subjects 0.00 (IQR: 0.00-0.01; overall P < 0.001). High LV %ID perfectly discriminated CMP from control subjects. Discrimination performance was similar for 18F-florbetapir LV %ID. Notably, for ATTRwt-CMP, LV %ID was higher with 124I-evuzamitide than 18F-florbetapir (P = 0.002). 124I-evuzamitide LV %ID was correlated with interventricular septum thickness (Spearman's ρ = 0.78) and LV global longitudinal strain (ρ = 0.54) from echocardiography, and with LV mass index (ρ = 0.82) and extracellular volume (ρ = 0.51) from cardiac magnetic resonance.

Conclusions: 124I-evuzamitide demonstrates uptake by cardiac amyloid and accurately discriminates amyloid CMP from control subjects. In AL-CMP, discrimination performance is similar to 18F-florbetapir. In ATTRwt-CMP, performance may be better with 124I-evuzamitide. Moderate-to-strong correlations of 124I-evuzamitide uptake with cardiac structural and functional metrics suggest valid amyloid quantification. Hence, 124I-evuzamitide is a promising novel radiotracer to detect and quantify cardiac amyloid.

Keywords

(124)I-evuzamitide ((124)I-p5+14); (18)F-florbetapir; AL amyloidosis; ATTR amyloidosis; cardiac amyloidosis.

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