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European Journal of Nuclear Medicine and Molecular Imaging

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01-08-2021 | Multiple Myeloma | Original Article

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

Authors: Cheng Wang, Yumei Chen, Yun Nan Hou, Qiufang Liu, Di Zhang, Haitao Zhao, You Zhang, Shuxian An, Lianghua Li, Jian Hou, Gang Huang, Jianjun Liu, Yong Juan Zhao, Weijun Wei

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2021

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 (t_1/2 = 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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Title: ImmunoPET imaging of multiple myeloma with [68Ga]Ga-NOTA-Nb1053
Authors: Cheng Wang
Yumei Chen
Yun Nan Hou
Qiufang Liu
Di Zhang
Haitao Zhao
You Zhang
Shuxian An
Lianghua Li
Jian Hou
Gang Huang
Jianjun Liu
Yong Juan Zhao
Weijun Wei
Publication date: 01-08-2021
Publisher: Springer Berlin Heidelberg
Keywords: Multiple Myeloma
Premedication
Daratumumab
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2021
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-021-05218-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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