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

Background: Cardiac amyloid quantification could advance early diagnosis of amyloid cardiomyopathy (CMP) and treatment monitoring. However, current imaging tools are based on indirect measurements. I-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 I-evuzamitide uptake and to compare its diagnostic value to F-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 I-evuzamitide and F-florbetapir. Control subjects underwent I-evuzamitide (n = 10) or F-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. I-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 F-florbetapir LV %ID. Notably, for ATTRwt-CMP, LV %ID was higher with I-evuzamitide than F-florbetapir (P = 0.002). I-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: I-evuzamitide demonstrates uptake by cardiac amyloid and accurately discriminates amyloid CMP from control subjects. In AL-CMP, discrimination performance is similar to F-florbetapir. In ATTRwt-CMP, performance may be better with I-evuzamitide. Moderate-to-strong correlations of I-evuzamitide uptake with cardiac structural and functional metrics suggest valid amyloid quantification. Hence, I-evuzamitide is a promising novel radiotracer to detect and quantify cardiac amyloid.