CD38-targeted Immuno-PET of Multiple Myeloma: From Xenograft Models to First-in-Human Imaging

Radiology. 2020 Jun;295(3):606-615. doi: 10.1148/radiol.2020192621. Epub 2020 Apr 7.


Background Current measurements of multiple myeloma disease burden are suboptimal. Daratumumab is a monoclonal antibody that targets CD38, an antigen expressed on nearly all myeloma cells. Purpose To demonstrate preclinical and first-in-human application of an antibody composed of the native daratumumab labeled with the positron-emitting radionuclide zirconium 89 (89Zr) through the chelator deferoxamine (DFO), or 89Zr-DFO-daratumumab, for immunologic PET imaging of multiple myeloma. Materials and Methods 89Zr-DFO-daratumumab was synthesized by conjugating 89Zr to daratumumab with DFO. A murine xenograft model using CD38-positive OPM2 multiple myeloma cells was used to evaluate CD38-specificity of 89Zr-DFO-daratumumab. Following successful preclinical imaging, a prospective phase I study of 10 patients with multiple myeloma was performed. Study participants received 74 MBq (2 mCi) of intravenous 89Zr-DFO-daratumumab. Each participant underwent four PET/CT scans over the next 8 days, as well as blood chemistry and whole-body counts, to determine safety, tracer biodistribution, pharmacokinetics, and radiation dosimetry. Because 89Zr has a half-life of 78 hours, only a single administration of tracer was needed to obtain all four PET/CT scans. Results 89Zr-DFO-daratumumab was synthesized with radiochemical purity greater than 99%. In the murine model, substantial bone marrow uptake was seen in OPM2 mice but not in healthy mice, consistent with CD38-targeted imaging of OPM2 multiple myeloma cells. In humans, 89Zr-DFO-daratumumab was safe and demonstrated acceptable dosimetry. 89Zr-DFO-daratumumab uptake was visualized at PET in sites of osseous myeloma. Conclusion These data demonstrate successful CD38-targeted immunologic PET imaging of multiple myeloma in a murine model and in humans. © RSNA, 2020 Online supplemental material is available for this article.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1*
  • Animals
  • Antibodies, Monoclonal
  • Bone Neoplasms / diagnostic imaging*
  • Deferoxamine
  • Disease Models, Animal*
  • Heterografts
  • Humans
  • Membrane Glycoproteins*
  • Multiple Myeloma / diagnostic imaging*
  • Positron Emission Tomography Computed Tomography / methods*
  • Prospective Studies
  • Sensitivity and Specificity
  • Tumor Burden
  • Zirconium


  • Antibodies, Monoclonal
  • Membrane Glycoproteins
  • daratumumab
  • Zirconium
  • CD38 protein, human
  • Cd38 protein, mouse
  • ADP-ribosyl Cyclase 1
  • Deferoxamine