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

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 ((89)Zr) through the chelator deferoxamine (DFO), or (89)Zr-DFO-daratumumab, for immunologic PET imaging of multiple myeloma. Materials and Methods (89)Zr-DFO-daratumumab was synthesized by conjugating (89)Zr to daratumumab with DFO. A murine xenograft model using CD38-positive OPM2 multiple myeloma cells was used to evaluate CD38-specificity of (89)Zr-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 (89)Zr-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 (89)Zr has a half-life of 78 hours, only a single administration of tracer was needed to obtain all four PET/CT scans. Results (89)Zr-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, (89)Zr-DFO-daratumumab was safe and demonstrated acceptable dosimetry. (89)Zr-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. (c) RSNA, 2020 Online supplemental material is available for this article.