Targeted ImmunoPET Scan Detects Multiple Myeloma Missed by Standard PET/CT

Standard imaging and blood tests may miss areas of active disease, potentially complicating diagnosis, treatment selection, and post-treatment assessment. This is particularly important when residual disease persists despite otherwise negative findings. Researchers have now developed a targeted immuno-positron emission tomography scan designed to detect myeloma that may be missed by standard testing.

The phase 2 clinical trial was led by Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine. The technology, known as immunoPET, uses radiolabeled antibodies that bind directly to myeloma cells. The study specifically evaluated ⁸⁹Zr-daratumumab for CD38-targeted immunoPET, which targets CD38, a surface protein expressed on myeloma cells.

Current standard-of-care monitoring often relies on positron emission tomography/computed tomography (PET/CT) using radiolabeled glucose. These scans detect areas where tumor cells take up more glucose than surrounding tissue. In multiple myeloma, however, this pattern is not always reliable, and standard PET/CT can miss residual disease in up to 40% of cases when abnormal glucose uptake is absent.

Researchers first evaluated the antibody-based approach in laboratory models with collaborators at Hoag Cancer Center before advancing it into early human studies and a multicenter phase 2 clinical trial. The trial enrolled 60 patients with multiple myeloma who underwent both standard glucose-based PET/CT and immunoPET.

More than 10% of patients had disease signals detected only by immunoPET, and follow-up biopsies confirmed that these findings represented active myeloma missed by standard PET/CT. Overall, immunoPET identified disease that standard PET/CT missed in 17 patients, or 28%, while standard PET/CT detected disease missed by immunoPET in 13 patients, or 22%. The two scans showed similar disease burden in the remaining patients, indicating that neither imaging approach detected every case.

The study was published in Radiology on November 3, 2026. A practical limitation of the current approach is that the antibody takes about one week to circulate through the body and bind to cancer cells. Researchers are therefore developing next-generation versions using smaller antibody fragments that could reach tumors more quickly and potentially enable same-day imaging.

“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. We are developing new and better technology designed to see where the disease is and make sure we are not missing it,” said C. Ola Landgren, M.D., Ph.D., chief of the Myeloma Division, director of Sylvester Myeloma Institute and senior author of the study.

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Sylvester Comprehensive Cancer Center