CD38-targeted immuno-PET of multiple myeloma: From xenograft models to first-in-human imaging

Gary A. Ulaner, Nicholas B. Sobol, Joseph A. O'Donoghue, Assen S. Kirov, Christopher C. Riedl, Ryan Min, Eric Smith, Lukas M. Carter, Serge K. Lyashchenko, Jason S. Lewis, C. Ola Landgren

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

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: Tese data demonstrate successful CD38-targeted immunologic PET imaging of multiple myeloma in a murine model and in humans.

Original languageEnglish (US)
Pages (from-to)606-615
Number of pages10
JournalRadiology
Volume295
Issue number3
DOIs
StatePublished - Jun 2020
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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