I-124 Evuzamitide PET/CT Highly Sensitive, Specific in Amyloid Detection

I-124 evuzamitide positron emission tomography (PET)/computed tomography (CT) scans are highly sensitive and specific for detecting cardiac amyloidosis, according to results from the REVEAL study.1

These data were presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026 in Phoenix, Arizona, by Mathew Maurer, MD, the Arnold and Arlene Goldstein Professor of Cardiology at Columbia University Irving Medical Center, Vagelos College of Physicians & Surgeons.1

“We think that this could be a very useful way to not only diagnose amyloid but diagnose it in a more sensitive and potentially more specific manner than currently available imaging,” Maurer told HCPLive in an exclusive interview. “And, importantly, at a time when the patient doesn’t have advanced cardiac amyloid, when drug therapy is most effective.”

REVEAL was a phase 3, open-label, multicenter study of I-124 evuzamitide as an imaging agent to diagnose cardiac amyloidosis. Patients were eligible for enrollment if they were suspected of having cardiac amyloidosis and were or would be undergoing a diagnostic evaluation for cardiac amyloidosis, among other criteria. Patients were excluded if they had an already established diagnosis of cardiac amyloidosis, were receiving therapy for amyloid transthyretin (ATTR) cardiac amyloidosis at enrollment, or had a myocardial infarction within 3 months of screening, among other criteria.2

Patients were administered a single dose of I-124 evuzamitide, which was administered intravenously. This was followed by oral potassium iodide for 3 days and a safety follow-up of 5 +/-2 and 30 +/- 5 days, at which point clinicians conducted safety blood tests. Standard-of-care tests were then undertaken up to day 60. The trial’s primary endpoint was the sensitivity and specificity of PET/CT images based on visual scan interpretation versus adjudicated diagnosis. The secondary endpoint was sensitivity and specificity by amyloid subtype.1

After taking PET/CT scans, the resulting images were de-identified and interpreted by 3 physicians with extensive experience, looking for the visual presence or absence of I-124 evuzamitide uptake. The standard-of-care diagnostic evaluations were interpreted by 3 amyloid expert physicians to determine diagnosis of cardiac amyloidosis based on current guideline recommendations. Both groups were blind to clinical data.1

A total of 195 patients were ultimately enrolled in the trial, of whom 170 received evuzamitide. Among these 170 patients, average NT-proBNP was 471 ng/L, while average LV wall thickness was 13 mm and LV ejection fraction was 57%. Additionally, 54 patients were confirmed to have ATTR, 21 had amyloid light-chain (AL), and 93 had no cardiac amyloidosis.1

Maurer and colleagues ultimately recorded an overall sensitivity of 93.5% (95% CI, 85.5-97.9; P <.0001) and a specificity of 86% (95% CI, 77.3-92.3; P <.0001) with I-124 evuzamitide. The negative prediction value was 94.1% (95% CI, 86.8-98.1) and the positive prediction value was 84.7%. Sensitivity was comparable among patients with ATTR (96.3%, 52 of 54) and AL (95.2%, 20 of 21). Additionally, evuzamitide PET outperformed bone scintigraphy in early ATTR, primarily in early, low-burden ATTR; 44% of PET-detected adjudicated ATTR had low natriuretic peptides or normal wall thickness, and 8 patients who were equivocal or negative on bone scintigraphy were detected by evuzamitide PET.1

Ultimately, Maurer and colleagues concluded that these data reflect evuzamitide PET scanning’s capacity to streamline heart failure amyloid evaluation and to identify early ATTR currently missed by imaging. While Maurer cites a handful of limitations inherent in the study’s structure, he is optimistic about the potential of this novel scanning technology.1

“We’re at a tipping point here where we can identify amyloid early,” Maurer said. “Amyloid is not pathologically normal, so it’s never normal to have amyloid in an organ, and as a result, we’ve been talking about earlier diagnosis for years, if not decades. This particular scanning technique could provide a real opportunity to improve outcomes for patients.”

Editors’ Note: Maurer reports disclosures with Alnylam, AstraZeneca, Bridge Bio, Ionis, Novo Nordisk, Pfizer, and others.

References

1. Maurer M, Masri A, Ezzeddine O, et al. 124I-Evuzamitide Amyloid-Targeted PET/CT: Detection of Early Cardiac Amyloidosis in a Prospective Multicenter Phase 3 Study Cohort. Presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026, Phoenix, AZ. October 9-12, 2026.

2. Sharmila Dorbala, Brigham and Women’s Hospital. REVEAL - Research With I-124 EVuzamitide to Elucidate Cardiac AmyLoidosis (REVEAL). ClinicalTrials.gov Identifier: NCT06788535. Updated April 30, 2026. Accessed October 16, 2026. https://clinicaltrials.gov/study/NCT06788535?term=NCT06788535&rank=1