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

Advanced Science

Nan Huo¹  Xiaojie Xu¹  Zhao Chen²  Yan Huo²  Cuicui Li²  Rongfu Wang²  Lei Kang²  Zachary T. Rosenkrans³  Carolina A. Ferreira⁴  Jonathan W. Engle⁴  Todd E. Barnhart⁴  Emily B. Ehlerding⁴  Dawei Jiang⁴  Weibo Cai⁴ 

[1] Department of Medical Molecular Biology Beijing Institute of Biotechnology Beijing 100850 China;Department of Nuclear Medicine Peking University First Hospital Beijing 100034 China;Department of Pharmaceutical Sciences University of Wisconsin – Madison Madison WI 53705 USA;Departments of Radiology and Medical Physics University of Wisconsin – Madison Madison WI 53705 USA;

关键词: CD38;    daratumumab;    Lu‐177;    lymphoma;    positron emission tomography (PET);    radioimmunotherapy;   

DOI  :  10.1002/advs.202001879

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown