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

Authors: Ulaner, G. A.; Sobol, N. B.; O'Donoghue, J. A.; Kirov, A. S.; Riedl, C. C.; Min, R.; Smith, E.; Carter, L. M.; Lyashchenko, S. K.; Lewis, J. S.; Landgren, C. O.
Article Title: CD38-targeted immuno-PET of multiple myeloma: From xenograft models to first-in-human imaging
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 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.
Journal Title: Radiology
Volume: 295
Issue: 3
ISSN: 0033-8419
Publisher: Radiological Society of North America, Inc.  
Date Published: 2020-06-01
Start Page: 606
End Page: 615
Language: English
DOI: 10.1148/radiol.2020192621
PUBMED: 32255416
PROVIDER: scopus
Notes: Article -- Export Date: 1 June 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. Christopher Riedl
    50 Riedl
  2. Gary Ulaner
    114 Ulaner
  3. Assen Kirov
    61 Kirov
  4. Jason S Lewis
    304 Lewis
  5. Eric Smith
    48 Smith
  6. Carl Ola Landgren
    250 Landgren
  7. Lukas M Carter
    18 Carter
  8. Nicholas Sobol
    5 Sobol
  9. Ryan Alexander Min
    1 Min