In their first-in-human targeted immunoPET study – published last week in the journal Radiology – scientists said they found active disease in patients which had been missed by standard PET/CT scans and blood tests, and which could help doctors more accurately map disease, guide treatment decisions and confirm whether cancer remains after therapy, they said.
The phase 2 clinical trial was led by a team from the Sylvester Comprehensive Cancer Centre, part of the University of Miami Miller School of Medicine.
Multiple myeloma can remain hidden in plain sight. This blood cancer grows in the bone marrow but spreads to many places in the body, and although doctors can use advanced imaging and newer blood tests to look for disease, these tests do not always tell the full story, which can affect everything from diagnosis to treatment decisions.
Now, the Sylvester researchers have shown that a targeted imaging approach can detect active myeloma that standard tests miss. The study used immunoPET, a new type of labelled antibodies that find and attach directly to myeloma cells.
“If we are going to cure multiple myeloma, we need two things. One, we need really effective medicines. Second, we need to be able to make sure there is no disease left behind after these treatments,” said Ola Landgren, MD, PhD, chief of the Myeloma Division, director of Sylvester Myeloma Institute, and senior author of the study. “We are developing new and better technology designed to see where the disease is and make sure we are not missing it.”
More than 36 000 Americans are diagnosed with multiple myeloma each year. In the current standard of care setting, their disease progression is tracked using standard PET/CT scans, which rely on labelled glucose. The standard PET/CT scans are based on the idea that tumour cells consume larger amounts of glucose than surrounding normal cells.
But for myeloma, this is not always true. In up to 40% of the cases, standard PET/CT scans miss residual disease because there is no abnormal glucose uptake.
“Myeloma cells frequently consume the same amount of glucose as the surrounding normal cells,” Landgren said. “It’s very well known among radiologists and myeloma experts that some patients who have myeloma in their bones may not light up on PET scans. The methods are simply not designed to reliably capture multiple myeloma.”
To find newer and better ways to identify myeloma cells, the researchers developed a new compound to trace the cancer cells. Specifically, they labelled antibodies that are designed to recognise a myeloma-specific surface protein called CD38. Landgren and collaborators at Hoag Cancer Centre first tested the idea in laboratory models before advancing it into early human studies and, now, a multicentre phase 2 clinical trial.
They enrolled 60 patients with multiple myeloma who underwent both a standard glucose-based PET/CT scan and their antibody-based scan, which they called immunoPET.
More than 10% of the patients showed disease signals only on the immunoPET scans. Follow-up biopsies confirmed that the immunoPET scan signals were active myeloma disease that the traditional PET/CT scans had missed.
For example, one patient had persistent back pain but normal blood markers and imaging. The immunoPET scan, however, revealed myeloma lesions in the spine. After the patient switched treatments, their pain resolved.
The technology also found myeloma cases that were far more extensive than expected. One patient had negative scans and blood tests, but the immunoPET scan found widespread disease. A follow-up biopsy confirmed it.
“Their standard tests showed no evidence of disease, but we found nearly 100 sites of myeloma throughout the body,” Landgren said. “These are exactly the kinds of patients who benefit from better scans.”
While in 17 patients (28%), immunoPET uncovered disease that standard PET/CT scans missed, the reverse was also true in 13 patients (22%). The two approaches detected a similar amount of disease in the remaining patients. No single imaging test identified every case of myeloma.
Rather than replacing existing tools, Landgren said, the goal is to add another layer of information. Together, blood tests, bone marrow biopsies and imaging each reveal important information.
“We show that you can successfully find much more disease,” Landgren said. “It’s a more sensitive and more precise technology, and we have very strong proof of principle that it works and that it’s meaningful.”
The current version of the scan still has limitations. For example, it takes a week for the antibody to travel through the body and attach to cancer cells, which makes administering the test more complicated.
Landgren and his colleagues are already developing next-generation versions, using smaller antibody fragments that can reach tumours more quickly. This could enable a same-day test, making it more practical for routine use.
Study details
Phase 2 Trial of 89Zr-Deferoxamine-Daratumumab for CD38-targeted Immuno-PET/CT Detection of Multiple Myeloma
Gary Ulaner, Russ Kuker, Benjamin Diamond et al.
Published in Radiology on 3 November 2026
Abstract
Background
Multiple myeloma (MM) imaging is currently suboptimal, which may limit patient care. Zirconium 89 (89Zr) deferoxamine (DFO)–daratumumab is a novel CD38-targeted immuno-PET tracer.
Purpose
To compare 89Zr-DFO-daratumumab PET/CT against standard-of-care fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT for detection of MM.
Materials and Methods
Participants with MM were accrued to this prospective phase 2 trial between March 2022 and July 2025. Standard-of-care 18F-FDG PET/CT and bone marrow biopsy were performed, along with research 89Zr-DFO-daratumumab PET/CT. If there were discrepant lesions between the two scans, image-guided biopsy was considered as the reference standard. The McNemar test was used to compare disease detection between the two imaging modalities.
Results
This study included 60 participants (median age, 63 years [IQR, 57–71 years]; 32 women). 89Zr-DFO-daratumumab PET/CT demonstrated at least one positive lesion in 43% (26 of 60; 95% CI: 31, 57) of participants, and 18F-FDG PET/CT demonstrated at least one positive lesion in 47% (28 of 60; 95% CI: 33, 60) of participants. While there was no overall difference in disease detection between the two imaging modalities (P = .81), MM was demonstrated only with 89Zr-DFO-daratumumab PET/CT in 13% (eight of 60) of participants, with subsequent biopsy confirmation of active myeloma.
Conclusion
In participants with MM, CD38-targeted 89Zr-DFO-daratumumab immuno-PET helped detect active myeloma in some participants with no signs of disease at 18F-FDG PET/CT.
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