Cardiac Imaging · Nuclear Cardiology

One Tracer, All Amyloid: The Evuzamitide and REVEAL Story

A pan-amyloid PET radiotracer just cleared its pivotal Phase III hurdle — here's what it could mean for a diagnosis that still takes years.

Clinical Review · Cardiovascular Imaging · Updated June 2026

The Diagnostic Gap

Despite growing physician awareness, cardiac amyloidosis remains substantially underdiagnosed.

Current estimates place the worldwide disease burden at roughly 400,000 patients, and that figure is widely considered an undercount.

A diagnostic journey of two to four years from first symptom to confirmed diagnosis remains common, often crossing several specialists and imaging studies before an answer emerges.

Part of the problem is structural, since today's noninvasive toolkit was never built to answer one question for every patient.

Bone-avid scintigraphy using technetium-99m pyrophosphate, DPD, or HMDP is highly specific for ATTR cardiac amyloidosis at Perugini grade 2 or 3, but its sensitivity for ATTR runs only around 70%, it cannot reliably identify AL amyloid, and a coexisting monoclonal protein forces a confirmatory biopsy regardless of how the scan looks.

Beta-amyloid PET tracers repurposed from Alzheimer's imaging, such as florbetapir and Pittsburgh compound B, can detect both AL and ATTR disease, but neither was designed around a structural feature shared by every amyloid subtype.

None of these established tools were built to quantify amyloid burden or track its change with treatment, a gap that matters more each year as ATTR stabilizers, gene silencers, and AL-directed therapies reshape how response is measured.

One Peptide, Every Amyloid Type

Evuzamitide, radiolabeled with iodine-124, is built around a synthetic 45-amino-acid peptide called p5+14 rather than around any single amyloid precursor protein.

The peptide folds into an alpha helix that aligns twelve positively charged lysine residues along one face, allowing electrostatic binding to the densely negative surface that essentially all amyloid fibrils share.

That same electrostatic logic extends to the heavily sulfated heparan sulfate proteoglycans that accompany amyloid deposits in tissue, a biochemical signature shown to be distinct from the lower-sulfated glycans found in healthy organs.

Because the binding target is structural rather than protein-specific, evuzamitide uptake has been documented across AL kappa, AL lambda, wild-type and variant ATTR, leukocyte chemotactic factor-2, gelsolin, apolipoprotein-A1, lysozyme, and serum amyloid A amyloidosis in human imaging studies.

In practical terms, the same single injection and scan can answer the detection question no matter which amyloid protein turns out to be the culprit.

What the Early Data Showed

The first-in-human Phase 1/2 study enrolled 50 patients with systemic amyloidosis alongside two asymptomatic ATTR variant carriers and five healthy controls.

Cardiac uptake was visually present in nearly every patient with known cardiac involvement and absent in every healthy control, translating into an overall sensitivity of 93.6% for amyloid detection.

A head-to-head pilot comparison against florbetapir found comparable diagnostic performance in AL cardiac amyloidosis but greater myocardial uptake with evuzamitide in ATTR disease, raising the possibility of an edge in the more common amyloid subtype.

Quantitative uptake also correlated with established markers of disease severity, including interventricular septal thickness, left ventricular mass index, global longitudinal strain, and extracellular volume on echocardiography and cardiac MRI.

Whole-body imaging additionally captured extracardiac amyloid in the kidney, liver, spleen, and soft tissue, which matters most in systemic AL disease, where multi-organ burden drives prognosis.

A published case report used serial evuzamitide PET to track falling cardiac amyloid burden in a patient with AL amyloidosis responding to plasma-cell-directed immunotherapy, hinting at a treatment-monitoring role that no currently available cardiac amyloid tracer fully offers.

The tracer's whole-body effective dose, about 9 mSv per standard 1 mCi injection, falls in the same range as routine PET myocardial perfusion imaging, and no drug-related serious adverse events or anti-peptide antibodies were observed.

REVEAL Brings It to Phase III

The pivotal REVEAL study moved evuzamitide from mechanistic promise to a prespecified, adequately powered diagnostic trial.

REVEAL enrolled 170 adults with suspected cardiac amyloidosis across 19 United States centers in a multicenter, open-label, single-arm design.

Each participant received one intravenous dose of evuzamitide followed by cardiac and partial-body PET/CT imaging three to five hours later, with scans read visually by cardiac PET physicians blinded to clinical data.

The reference standard was an independent, blinded adjudication of standard-of-care diagnosis using each center's routine clinical workup, completed within 60 days of the scan.

The trial's prespecified hypothesis was that visual evuzamitide PET would exceed 65% sensitivity and 55% specificity for cardiac amyloidosis against that standard-of-care reference, with secondary analyses planned separately for ATTR and AL subtypes.

In May 2026, the sponsor announced that REVEAL met both primary endpoints — sensitivity and specificity for visual diagnosis of cardiac amyloidosis — though specific point estimates have not yet been released pending presentation at a scientific congress.

Evuzamitide carries FDA Breakthrough Therapy Designation for cardiac amyloidosis imaging and Orphan Drug status for both AL and ATTR amyloidosis in the United States and European Union, and the sponsor has indicated plans to discuss regulatory submission with health authorities following REVEAL.

It remains an investigational compound that has not been approved by any regulatory authority for any indication, and the topline data summarized above have not yet undergone peer review.

Table 1. Cardiac amyloidosis imaging tools at a glance

Modality	AL detection	ATTR detection	Quantifies burden	Monoclonal protein issue	Whole-body imaging
⁹⁹ᵐTc-PYP / DPD / HMDP scintigraphy	Not validated	Yes — ~70% sensitivity at Perugini 2–3	Semi-quantitative grade only	Biopsy required if present	No
¹⁸F-florbetapir / ¹¹C-PiB (β-amyloid PET)	Yes	Yes — generally lower uptake than ATTR-specific tracers	Yes (SUV / retention index)	Not a confounder	Yes
¹²⁴I-evuzamitide (pan-amyloid PET)	Yes	Yes — comparable to or greater than florbetapir	Yes	Not a confounder	Yes, whole-body

Table 2. Evuzamitide development snapshot

Milestone	Status
Orphan Drug status (AL & ATTR, US/EU)	Granted
FDA Breakthrough Therapy Designation	Granted, August 2024
Phase 1/2 first-in-human study	93.6% sensitivity in 50 amyloidosis patients
Phase III REVEAL study	170 adults, 19 US centers — completed
REVEAL topline results	Primary endpoints met, May 2026
Full REVEAL dataset	Pending presentation at scientific congress
Regulatory submission	Discussions planned with FDA and other health authorities
Companion SPECT tracer (⁹⁹ᵐTc-p5+14)	Same peptide platform, investigational

Case Vignette

A 78-year-old man presents with progressive exertional dyspnea and bilateral lower-extremity edema, and his echocardiogram shows increased left ventricular wall thickness with preserved ejection fraction.

Serum free light chain testing reveals a small monoclonal kappa elevation, and bone scintigraphy shows grade 2 myocardial tracer uptake.

Under current diagnostic rules, the presence of a monoclonal protein invalidates scintigraphy as a stand-alone test, so guideline-directed workup still requires an endomyocardial or fat-pad biopsy with mass spectrometry typing before a treatment pathway — ATTR stabilizer versus AL-directed chemotherapy — can be chosen with confidence.

A pan-amyloid PET tracer is designed for exactly this scenario, since the same scan that confirms amyloid deposition is present, regardless of fibril type, could in principle pair with light-chain typing to support a faster diagnosis while also revealing whether amyloid extends beyond the heart.

Where It Could Fit: A Proposed Algorithm

No society has written evuzamitide into a guideline yet, so what follows is an illustrative algorithm built from the current ESC-style nonbiopsy pathway, not an endorsed clinical pathway.

The logic rests on one mechanistic limit worth stating up front: a pan-amyloid signal confirms that amyloid is present, but it does not by itself prove which protein is depositing it, so light-chain and genetic testing stay in the loop.

The proposed insertion point is at the imaging step itself, either replacing bone scintigraphy as the initial confirmatory scan or, more conservatively, serving as a problem-solver wherever scintigraphy and serology disagree.

Established step today Proposed evuzamitide step, if approved Decision point / biopsy trigger

Step 1 · Today
Clinical suspicion of cardiac amyloidosis — HFpEF, unexplained LV wall thickening, ECG–echo voltage discordance, low-flow low-gradient severe aortic stenosis, bilateral carpal tunnel syndrome, or a family history of ATTR.

Step 2 · Today
Order together: echo/cardiac MRI characterization and serum/urine immunofixation with free light chains, to screen for a monoclonal protein before any imaging result is interpreted.

Step 3 · If approved
Pan-amyloid PET (evuzamitide) performed as the confirmatory cardiac scan, in place of or alongside bone scintigraphy, with whole-body acquisition to flag extracardiac uptake in the same sitting.

PET negative

Cardiac amyloidosis effectively excluded given the tracer's high sensitivity in early studies — pursue alternative causes of hypertrophy or heart failure, and biopsy is generally avoided.

PET positive, no monoclonal protein

ATTR cardiac amyloidosis is highly likely without further tissue confirmation — proceed directly to TTR genotyping to separate wild-type from variant disease, then start ATTR-directed therapy.

PET positive, monoclonal protein present

Subtype remains indeterminate — could be ATTR-CA with incidental MGUS, or true AL-CA — so endomyocardial or fat-pad biopsy with mass spectrometry typing is still required before committing to a treatment pathway.

PET equivocal or discordant with prior scintigraphy

Correlate with CMR late gadolinium enhancement and extracellular volume, or refer to a specialized amyloidosis center; biopsy if the picture stays unresolved.

Step 4 · If approved & validated
Serial evuzamitide PET after diagnosis and treatment initiation, to quantify change in myocardial amyloid burden alongside NT-proBNP, troponin, and free light chains — a monitoring function no current cardiac amyloid tracer offers.

Two deployment models are realistic, and the sponsor's own language leans toward the second: evuzamitide could become the front-line confirmatory scan for every patient with suspected cardiac amyloidosis, or it could enter more conservatively as a second-tier tool reserved for the indeterminate scintigraphy-plus-serology combinations that drive biopsy referrals today.

Which model wins out will depend on the subtype-specific sensitivity and specificity from the full REVEAL dataset, the wording of any eventual FDA label, and whether cardiology and nuclear medicine societies choose to revise their nonbiopsy diagnostic algorithms once that data is public.

Why It Matters for Practice

If the full REVEAL dataset confirms the topline signal, the clinical case for a single, subtype-agnostic test becomes straightforward to articulate to patients and referring colleagues alike.

A tracer that performs across AL and ATTR disease could shorten the diagnostic odyssey for patients whose presentation does not fit cleanly into either established pathway, particularly those with a coincidental monoclonal protein or an atypical TTR variant.

The same quantitative, whole-body readout that detects disease could eventually support staging extracardiac involvement and tracking treatment response over time, functions that current bone-avid and beta-amyloid tracers were not built to deliver.

None of this changes today's guideline-based workflow, and scintigraphy plus monoclonal protein screening remains the standard first step until evuzamitide, if approved, earns a defined place in that algorithm.

Bottom Line

• Evuzamitide is a pan-amyloid PET radiotracer designed to detect AL, ATTR, and rarer amyloid subtypes with a single test, addressing a gap no existing cardiac amyloid imaging tool fully closes.
• Phase 1/2 data showed 93.6% sensitivity for amyloid detection, and the pivotal Phase III REVEAL trial has now met its prespecified primary endpoints for sensitivity and specificity against standard-of-care diagnosis.
• It remains investigational, the full REVEAL dataset is still unpublished, and it is not yet available for clinical use while the sponsor pursues regulatory submission.
• If approved, its quantitative, whole-body, subtype-agnostic profile could reshape how clinicians detect, differentiate, and monitor cardiac amyloidosis in everyday practice.

References

1. Bayer. Investigational PET Tracer Iodine 124 Evuzamitide from Bayer Met Primary Endpoints in Phase III Study in Patients Suspected to Have Cardiac Amyloidosis.
2. Diagnostic and Interventional Cardiology (DAIC). Positive Topline Data for Investigational PET Tracer for Cardiac Amyloidosis.
3. ClinicalTrials.gov. Research With I-124 Evuzamitide to Elucidate Cardiac Amyloidosis (REVEAL), NCT06788535.
4. Heart Failure Reviews. Positron Emission Tomography in Cardiac Amyloidosis: Current Evidence and Future Directions.
5. Pharmaceuticals (MDPI). Pan-Amyloid Reactive Peptides p5+14 and p5R Exhibit Specific Charge-Dependent Binding to Glycosaminoglycans.
6. American Society of Nuclear Cardiology, Imaging Insights. Pan-Amyloid Tracers Coming! How Will They Change the Landscape?

For physician education only. Evuzamitide is investigational and is not approved by the FDA, EMA, or any other regulatory authority for any indication. Topline trial results discussed here have not undergone peer review and are subject to change upon full data publication.