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ImmunoPET imaging of multiple myeloma with [68Ga]Ga-NOTA-Nb1053

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

An Editorial to this article was published on 03 May 2021

Abstract

Purpose

Multiple myeloma (MM) remains incurable and its diagnosis relies heavily on bone marrow aspiration and biopsy. CD38 is a glycoprotein highly specific for MM. Antibody therapeutics (e.g., daratumumab) targeting CD38 have shown encouraging efficacy in treating MM, either as a monotherapy agent or in combination with other regimens. However, efficient stratification of patients who might benefit from daratumumab therapy and timely monitoring of the therapeutic responses are still clinical challenges. This work aims to devise a CD38-targeted imaging strategy and assess its value in diagnosing MMs.

Methods

By labeling a CD38-specific single domain antibody (Nb1053) with 68Ga (t1/2 = 1.1 h), we developed a CD38-targeted immuno-positron emission tomography (immunoPET) imaging probe [68Ga]Ga-NOTA-Nb1053. The probe was developed with good radiochemical yield (> 50%), excellent radiochemical purity (> 99%), and immunoreactivity (> 95%). The diagnostic accuracy of the probe was thoroughly investigated in preclinical MM models.

Results

ImmunoPET imaging with [68Ga]Ga-NOTA-Nb1053 specifically depicted all the subcutaneous and orthotopic MM lesions, outperforming the traditional 18F-fluorodeoxyglucose PET and the nonspecific [68Ga]Ga-NOTA-NbGFP immunoPET. More importantly, daratumumab preloading significantly reduced [68Ga]Ga-NOTA-Nb1053 uptake in the disseminated bone lesions, indicating the overlapping targeting epitopes of [68Ga]Ga-NOTA-Nb1053 with that of daratumumab. Furthermore, premedication with sodium maleate or fructose significantly decreased kidney retention of [68Ga]Ga-NOTA-Nb1053 and improved the diagnostic value of the probe in lymphoma models.

Conclusion

This work successfully developed a novel CD38-targeted immunoPET imaging approach that enabled precise visualization of CD38 and diagnosis of MMs. Upon clinical translation, [68Ga]Ga-NOTA-Nb1053 immunoPET may serve as a valuable CD38-targeted molecular imaging toolbox, facilitating early diagnosis of MM and precise assessment of the therapeutic responses.

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Data availability

All the raw data and materials involved in the work can be obtained from Prof. Wei upon rational request.

Code availability

Not applicable.

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Acknowledgements

The authors want to thank all the clinical and research staff at the Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University for their technical assistance and helpful discussions.

Funding

This work was supported in part by the National Key Research and Development Program of China (Grant No. 2020YFA0909000), National Natural Science Foundation of China (Grant Nos. 81771858, 81830052, 81530053, 31871403, and 82001878), Shanghai Key Laboratory of Molecular Imaging (Grant No. 18DZ2260400), Shanghai Rising-Star Program (Grant No. 20QA1406100), Foundation for Basic Research of Science and Technology Project in Shenzhen (Grant No. JCYJ20190808163411340), Construction Project of Shanghai Key Laboratory of Molecular Imaging (Grant No. 18DZ2260400), and Shanghai Municipal Education Commission (Class II Plateau Disciplinary Construction Program of Medical Technology of SUMHS, 2018–2020).

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Author notes

  1. Cheng Wang and Yumei Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China

    Cheng Wang, Yumei Chen, Di Zhang, Haitao Zhao, You Zhang, Shuxian An, Lianghua Li, Gang Huang, Jianjun Liu & Weijun Wei

  2. State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China

    Yun Nan Hou & Yong Juan Zhao

  3. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China

    Qiufang Liu

  4. Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Jian Hou

  5. Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, China

    Gang Huang

  6. Ciechanover Institute of Precision and Regenerative Medicine, School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, 518172, China

    Yong Juan Zhao

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  1. Cheng Wang
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Contributions

W. Wei, J. Liu, and Y. J. Zhao collaboratively conceived and designed the project. C. Wang, Y. Chen, W. Wei, Q. Liu, and D. Zhang performed the experiments and wrote most of the manuscript. Y. N. Hou produced the sdAbs and contributed to the writing. S. An, Y. Zhang, and H. Zhao helped in the radiolabeling and characterization of the radiotracers. J. Hou and G. Huang provided inputs in the initial design of the project and revised the manuscript. W. Wei, J. Liu, and Y. J. Zhao supervised the study, revised, and finalized the manuscript.

Corresponding authors

Correspondence to Jianjun Liu, Yong Juan Zhao or Weijun Wei.

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Conflict of interest

W. Wei and J. Liu are co-inventors on a provisional patent application (Application No. 202011131233.7) encompassing the technology described in this manuscript.

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Wang, C., Chen, Y., Hou, Y.N. et al. ImmunoPET imaging of multiple myeloma with [68Ga]Ga-NOTA-Nb1053. Eur J Nucl Med Mol Imaging 48, 2749–2760 (2021). https://doi.org/10.1007/s00259-021-05218-1

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