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

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.

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.

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.

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.

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.