CD38-Targeted Theranostics of Lymphoma with 89Zr/177Lu-Labeled Daratumumab.

Abstract

Lymphoma is a heterogeneous disease with varying clinical manifestations and outcomes. Many subtypes of lymphoma, such as Burkitt's lymphoma and diffuse large B cell lymphoma, are highly aggressive with dismal prognosis even after conventional chemotherapy and radiotherapy. As such, exploring specific biomarkers for lymphoma is of high clinical significance. Herein, a potential marker, CD38, is investigated for differentiating lymphoma. A CD38-targeting monoclonal antibody (mAb, daratumumab) is then radiolabeled with Zr-89 and Lu-177 for theranostic applications. As the diagnostic component, the Zr-89-labeled mAb is highly specific in delineating CD38-positive lymphoma via positron emission tomography (PET) imaging, while the Lu-177-labeled mAb serves well as the therapeutic component to suppress tumor growth after a one-time administration. These results strongly suggest that CD38 is a lymphoma-specific marker and prove that 89Zr/177Lu-labeled daratumumab facilitates immunoPET imaging and radioimmunotherapy of lymphoma in preclinical models. Further clinical evaluation and translation of this CD38-targeted theranostics may be of significant help in lymphoma patient stratification and management.

• Authors: Lei Kang, Cuicui Li, Zachary T Rosenkrans, Nan Huo, Zhao Chen, Emily B Ehlerding, Yan Huo, Carolina A Ferreira, Todd E Barnhart, Jonathan W Engle, Rongfu Wang, Dawei Jiang, Xiaojie Xu, Weibo Cai
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 8 Issue 10 Pg. 2001879 (05 2021) ISSN: 2198-3844 [Electronic] Germany
• PMID: 34026426 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.

Chemical References

• Antibodies, Monoclonal
• Immunologic Factors
• Membrane Glycoproteins
• Radioisotopes
• Radiopharmaceuticals
• daratumumab
• Lutetium
• Lutetium-177
• Zirconium
• CD38 protein, human
• ADP-ribosyl Cyclase 1
• Zirconium-89

Topics

• ADP-ribosyl Cyclase 1 (immunology, metabolism)
• Animals
• Antibodies, Monoclonal (pharmacokinetics, pharmacology)
• Cell Line, Tumor
• Humans
• Immunologic Factors (pharmacokinetics)
• Lutetium (pharmacokinetics)
• Lymphoma, Large B-Cell, Diffuse (drug therapy, immunology, pathology)
• Membrane Glycoproteins (immunology, metabolism)
• Mice, Inbred BALB C
• Mice, SCID
• Positron Emission Tomography Computed Tomography (methods)
• Precision Medicine (methods)
• Radioisotopes (pharmacokinetics)
• Radiopharmaceuticals (pharmacokinetics, pharmacology)
• Tissue Distribution
• Xenograft Model Antitumor Assays
• Zirconium (pharmacokinetics)
• Mice