REVEAL: I-124 Evuzamitide PET/CT Specific, Sensitive for Cardiac Amyloidosis Diagnosis

I-124 evuzamitide positron emission tomography (PET)/computed tomography (CT) is both highly sensitive and specific in diagnosing cardiac amyloidosis while maintaining an acceptable safety profile.1

Presented at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, by Sharmila Dorbala, MD, MPH, director of nuclear cardiology at Brigham and Women’s Hospital and director of amyloidosis research at Mass General Brigham Heart & Vascular Institute, these data represent the culmination of the phase 3 REVEAL trial.1

“I think this is a huge leap from the previous scenario, where we had multiple complex tests interpreted by different folks,” Dorbala told HCPLive in an exclusive interview. “With this particular approach, it doesn’t matter where the patient goes, but if cardiac amyloid is in the differential and you perform a PET scan, you may be able to detect amyloid deposits in multiple organ systems. Therefore, this approach can potentially reduce the time to diagnosis significantly.”

REVEAL was an open-label multicenter evaluation of I-124 evuzamitide as a PET imaging agent. Dorbala and colleagues enrolled patients ≥18 years of age who were suspected of having cardiac amyloidosis and were or would undergo a diagnostic evaluation of any kind. Patients were excluded if they had an established diagnosis of cardiac amyloidosis or systemic amyloidosis with known organ involvement, among other criteria.2

The trial was divided into a primary and safety analysis and an image-evaluable analysis. The primary endpoints of the study were the specificity and sensitivity of PET/CT imaging with I-124 evuzamitide ≤60 days following administration based on visual scan interpretations. Secondary endpoints included specificity and sensitivity for the diagnosis of ATTR amyloidosis and AL amyloidosis, as well as the incidence of treatment-emergent adverse events ≤30 days after administration.2

A total of 195 patients were enrolled at 18 sites across the US, of whom 170 were ultimately included in the safety and intent-to-image cohorts following administration and PET/CT imaging. Of these patients, 76 (44.7%) had cardiac amyloidosis – 54 with ATTR, 21 with light chain, and 1 with indeterminate type – and 93 *54.7%) did not, based on the truth standard consensus.3

Dorbala and colleagues found that overall majority-decision sensitivity was 94% (95% CI, 85-98%), while specificity was 86% (95% CI, 77-92%). Positive predictive value was 85% (95% CI, 75-92%), and negative predictive value was 94% (95% CI, 87-98%). All 4 values were consistent across the individual readers. Additionally, the secondary endpoints in ATTR and AL amyloidosis also met the predefined success criteria – among the 54 patients with confirmed ATTR amyloidosis, 52 had positive imaging by majority decision, and of the 21 with AL amyloidosis, 20 had positive imaging.3

Among the 170 patients receiving I-124 evuzamitide, 55 (32.4%) exhibited ≥1 treatment-emergent adverse event by day 30. Of these patients, 11 (6.5%) had a serious event, and only 1 – fatigue – was considered relevant to the treatment. Additionally, no deaths occurred during the study period, and none of the serious adverse events were related to I-124 evuzamitide.3

Ultimately, Dorbala and colleagues concluded that this imaging strategy is extremely effective in identifying these patients, with an excellent safety profile and substantial specificity and sensitivity. Dorbala also expressed excitement for the future of amyloidosis treatment following this trial, as she believes it demonstrates a significant step forward in diagnosis that will allow for more focus on treatment.1

“In order to do all of this, we will need to perform randomized clinical trials of treatment in these patients to see what the optimal time is to initiate therapy in some of these patients who don’t have symptoms or who don’t have changes on echo or MRI,” Dorbala said. “It’s a very exciting time for the field to be able to, as a first step, detect these early deposits, but the future is going to be more exciting, since we’ll need more trials to study whether we can prevent cardiac amyloid heart failure by early therapy.”

Editors’ Note: Dorbala reports disclosures with Attralus, AstraZeneca, BridgeBio, GE Healthcare, Medtrace, Pfizer, and others.

References

1. Dorbala S. A Phase 3 Clinical Trial of I124-evuzamitide to Diagnose Cardiac Amyloidosis. Presented at the European Society of Cardiology (ESC) Congress 2026, Munich, Germany. August 28-31, 2026.

2. Dorbala S. REVEAL – Research With I-124 EVuzamitide to Elucidate Cardiac AmyLoidosis (REVEAL). ClinicalTrials.gov Identifier: NCT06788535. Updated April 30, 2026. Accessed September 8, 2026. https://clinicaltrials.gov/study/NCT06788535

3. Dorbala S, Maurer MS, Cuddy SA, et al. I-124 evuzamitide positron emission tomography/computed tomography for diagnosing cardiac amyloidosis. JAMA. Published online August 30, 2026. doi:10.1001/jama.2026.17361