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Potential of three-step pretargeting radioimmunotherapy using biotinylated bevacizumab and succinylated streptavidin in triple-negative breast cancer xenograft

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Abstract

Objective

Pretargeting radioimmunotherapy (PRIT) is a promising approach that can reduce long-time retention of blood radioactivity and consequently reduce hematotoxicity. Among the PRIT strategies, the combination of biotin-conjugated mAb and radiolabeled streptavidin (StAv) is a simple and convenient method because of its ease of preparation. This study performed three-step (3-step) PRIT using the sequential injection of (1) biotinylated bevacizumab (Bt-BV), (2) avidin, and (3) radiolabeled StAv for the treatment of triple-negative breast cancer (TNBC).

Methods

Four biodistribution studies were performed using 111In in tumor-bearing mice to optimize each step of our PRIT methods. Further, a therapeutic study was performed with optimized 3-step PRIT using 90Y-labeled StAv.

Results

Based on the biodistribution studies, the protein dose of Bt-BV and avidin was optimized to 100 μg and 10 molar equivalent of BV, respectively. Succinylation of StAv significantly decreased the kidney accumulation level (with succinylation (6.96 ± 0.91) vs without succinylation (20.60 ± 1.47) at 1 h after injection, p < 0.0001) with little effect on the tumor accumulation level. In the therapeutic study, tumor growth was significantly suppressed in treatment groups with optimized 3-step PRIT using 90Y-labeled succinylated StAv compared to that of the no-treatment group (p < 0.05).

Conclusions

The 3-step PRIT strategy of this study achieved fast blood clearance and low kidney uptake with little effect on the tumor accumulation level, and a certain degree of therapeutic effect was consequently observed. These results indicated that the pretargeting treatment of the current study may be effective for human TNBC treatment.

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Acknowledgements

The authors have no conflicts of interest to declare. This work was supported by a JSPS KAKENHI grant (No. 16K10269).

Funding

This work was supported by a JSPS KAKENHI grant (No. 16K10269).

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Author notes

  1. Wenchao Gu and Ryan Yudistiro these authors contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan

    Wenchao Gu, Ryan Yudistiro, Natsumi Katsumata & Yoshito Tsushima

  2. Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, 371-8511, Japan

    Hirofumi Hanaoka

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  1. Wenchao Gu
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  2. Ryan Yudistiro
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  3. Hirofumi Hanaoka
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Correspondence to Hirofumi Hanaoka.

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Gu, W., Yudistiro, R., Hanaoka, H. et al. Potential of three-step pretargeting radioimmunotherapy using biotinylated bevacizumab and succinylated streptavidin in triple-negative breast cancer xenograft. Ann Nucl Med 35, 514–522 (2021). https://doi.org/10.1007/s12149-021-01597-5

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  • DOI: https://doi.org/10.1007/s12149-021-01597-5

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