Immuno-PET/CT detects myeloma missed by FDG-PET/CT

Immuno-PET/CT using an investigational CD38-targeted radiotracer detected multiple myeloma in 13% of patients who tested negative on standard F-18 FDG-PET/CT scans, according to results of a phase II trial published November 3 in Radiology. 

A team from Hoag Family Cancer Institute in Irvine, CA, and the Sylvester Comprehensive Cancer Center at the University of Miami evaluated zirconium-89 (Zr-89) deferoxamine (DFO)-daratumumab PET/CT alongside F-18 FDG-PET/CT in patients with multiple myeloma, with findings suggesting the investigational tracer could eventually fill a gap in care. 

"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 senior author C. Ola Landgren, MD, PhD, of the University of Miami, in a news release from the school. “We are developing new and better technology designed to see where the disease is and make sure we are not missing it.” 

Standard FDG PET/CT misses active multiple myeloma in 30% to 50% of patients with biopsy-proven disease because myeloma cells have low glucose uptake, Landgren and colleagues explained. Daratumumab is an anti-CD38 monoclonal antibody U.S.-approved for multiple myeloma treatment. It targets CD38, a protein overexpressed on myeloma cells, and can be radiolabeled with Zr-89 to form an immuno-PET radiotracer. 

In the first-in-human phase I trial, the researchers determined an optimal Zr-89 DFO-daratumumab dose of 2 mCi and radiotracer uptake time of 6 to 7 days. In the phase II trial, they prospectively enrolled 60 adults (median age, 63 years old; 32 women) at their two centers between March 2022 and July 2025. All participants underwent Zr-89–DFO-daratumumab PET/CT and F-18 FDG-PET/CT at the same time point without intervening therapy. The primary outcome was the proportion of participants with at least one detected lesion on each scan.

Images in a 69-year-old man with multiple myeloma detected with Zr-89 deferoxamine (DFO)-daratumumab PET but not with F-18 FDG-PET. (A) Maximum intensity projection image from F-18 FDG-PET/CT shows no foci of disease. Physiologic F-18 FDG uptake is seen in the brain, blood pool, liver, and urinary tract. (B) Maximum intensity projection image from Zr-89 DFO-daratumumab PET/CT demonstrates more than 100 foci that are localized to bone (arrows), consistent with osseous myeloma. Physiologic uptake is seen in the liver and spleen. Sagittal (C) CT, (D) Zr-89 DFO-daratumumab PET, and (E) fused Zr-89 DFO-daratumumab PET/CT images demonstrate localization of multiple foci to bone. Subsequent biopsy of the right ilium confirmed active CD38-positive myeloma. Color bars show standardized uptake value. RSNAAccording to the results, Zr-89–DFO–daratumumab identified at least one positive lesion in 43% of participants (26 of 60), compared with 47% for F-18 FDG-PET/CT (28 of 60), with no significant overall difference (P = .81). However, Zr-89–DFO–daratumumab detected disease in 13% of participants (eight of 60) whose F-18 FDG scans were negative, with active myeloma confirmed on biopsy in all eight cases. Severe adverse events were not observed, while nonsevere events occurred in 5% of participants (three of 60). 

"This proof-of-principle clinical study demonstrates the utility of identifying [multiple myeloma] lesions using an immuno-PET radiotracer that targets the CD38 cell surface antigen, even in some patients with negative F-18 FDG PET/CT scans," the group wrote. 

Ongoing research is examining the radiotracer’s utility for detecting residual disease after treatment and predicting response to CD38-targeted therapies, the group noted. The authors also highlighted its potential role in CD38-targeted radioligand therapy, where daratumumab could be linked to therapeutic isotopes such as lutetium-177 or actinium-225. 

The full study is available here.