A novel theranostic probe [111In]In-DO3A-NHS-nimotuzumab in glioma xenograft

Yu Tang; Zhonghui Liao; Feize Li; Weihao Liu; Jing Gao; Yuhao Li; Yingjiang Hu; Huawei Cai; Huan Ma; Yuanyou Yang; Jijun Yang; Jiali Liao; Ning Liu

doi:10.1515/ract-2021-1064

Article

A novel theranostic probe [¹¹¹In]In-DO3A-NHS-nimotuzumab in glioma xenograft

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Published/Copyright: April 5, 2022

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From the journal Radiochimica Acta Volume 110 Issue 5

Abstract

Indium-¹¹¹ (¹¹¹In) has an appropriate half-life (T_1/2 = 67 h) and energy characteristics for cancer diagnosis via γ-ray imaging and cancer therapy with Auger electrons. The aim of our study is to evaluate the potential of [¹¹¹In]In-DO3A-NHS-nimotuzumab as a theranostic agent for radioimmunoimaging (RII) and radioimmunotherapy (RIT) against human glioma xenografts in mice. We explored the chelators DO3A-NHS and DOTA-p-SCN-Bz to optimize ¹¹¹In radiolabeling efficiency of nimotuzumab. The radiopharmaceuticals were purified by PD-10 mini-column and their in vitro stabilities were assessed. We investigated the biodistribution of [¹¹¹In]In-DO3A-NHS-nimotuzumab as it had relatively superior labeling efficiency and stability in vitro. We conducted SPECT imaging on mice bearing glioma (U87MG) xenografts, which were injected with ∼3.7 MBq of [¹¹¹In]In-DO3A-NHS-nimotuzumab. The in vivo radiotherapeutic effects of [¹¹¹In]In-DO3A-NHS-nimotuzumab was analyzed via injecting a single 37 MBq dose, 2 × 18 MBq doses, or 2 × 37 MBq doses into mice bearing U87MG xenografts. The control groups were administered either 30 μg nimotuzumab or saline. The radiochemical yields of [¹¹¹In]In-DO3A-NHS-nimotuzumab and [¹¹¹In]In-DOTA-p-SCN-Bz-nimotuzumab were > 85% and > 75%, respectively. [¹¹¹In]In-DO3A-NHS-nimotuzumab had > 95% radiochemical purity and was more stable in vitro than [¹¹¹In]In-DOTA-p-SCN-Bz-nimotuzumab. Biodistribution study demonstrated that [¹¹¹In]In-DO3A-NHS-nimotuzumab was highly stable in vivo. SPECT imaging disclosed that [¹¹¹In]In-DO3A-NHS-nimotuzumab had excellent targeted tumor uptake and retained in tumors for 24 and 72 h. All [¹¹¹In]In-DO3A-NHS-nimotuzumab treatments substantially inhibited tumor growth over the controls. The 2 × 37 MBq treatment was particularly efficacious, and presented with survival time prolonged by ≤66 days. In contrast, the survival time of the control group was only 30 days. In our study, we developed an optimized synthesis protocol for radiopharmaceutical ¹¹¹In-DO3A-NHS-nimotuzumab and demonstrated that it is a promising theranostic agent. It could be highly efficacious in RII and RIT against EGFR-expressing glioma.

Keywords: EGFR; glioma; SPECT imaging; treatment; [111In]In-DO3A-NHS-nimotuzumab

Corresponding author: Yuanyou Yang and Ning Liu, Key Laboratory of Radiation Physics and Technology of Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, P. R. China, E-mail: yangyy@scu.edu.cn (Y. Yang), nliu720@scu.edu.cn (N. Liu)

Funding source: Key Research Development Project of Sichuan Provincial Department of Science and Technology

Award Identifier / Grant number: (No. 2018SZ0022)

Funding source: Major Science and Technology Projects of Sichuan Province (China)

Award Identifier / Grant number: (No. 2019ZDZX0004)

Funding source: Strategic Cooperation Project of Luzhou Municipal People’s Government of Sichuan University

Award Identifier / Grant number: (No. 2018CDLZ-09)

Funding source: Open Program of Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province

Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was financially supported by the Key Research Development Project of Sichuan Provincial Department of Science and Technology (No. 2018SZ0022), the Major Science and Technology Projects of Sichuan Province (China) (No. 2019ZDZX0004), the Strategic Cooperation Project of Luzhou Municipal People’s Government of Sichuan University (No. 2018CDLZ-09), and the Open Program of Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province.
Conflict of interest statement: The authors report no conflict of interest.

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Received: 2021-06-09

Revised: 2022-03-17

Accepted: 2022-03-18

Published Online: 2022-04-05

Published in Print: 2022-05-25

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https://doi.org/10.1515/ract-2021-1064

Keywords for this article

EGFR; glioma; SPECT imaging; treatment; [111In]In-DO3A-NHS-nimotuzumab