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

Adv Sci (Weinh). 2021 Mar 15;8(10):2001879. doi: 10.1002/advs.202001879. eCollection 2021 May.

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.

Keywords: CD38; Lu‐177; daratumumab; lymphoma; positron emission tomography (PET); radioimmunotherapy; theranostics.

Publication types

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

MeSH terms

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

Substances

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