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Article

Preclinical Evaluation of Podoplanin-Targeted Alpha-Radioimmunotherapy with the Novel Antibody NZ-16 for Malignant Mesothelioma

by
Hitomi Sudo
1,
Atsushi B. Tsuji
1,*,
Aya Sugyo
1,
Mika K. Kaneko
2,
Yukinari Kato
2,3,
Kotaro Nagatsu
4,
Hisashi Suzuki
4 and
Tatsuya Higashi
1
1
Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science (iQMS), National Institutes for Quantum and Radiological Science and Technology (QST), 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan
2
Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
3
Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
4
Department of Advanced Nuclear Medicine Science, Institute for Quantum Medical Science (iQMS), National Institutes for Quantum and Radiological Science and Technology (QST), 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan
*
Author to whom correspondence should be addressed.
Cells 2021, 10(10), 2503; https://doi.org/10.3390/cells10102503
Submission received: 6 August 2021 / Revised: 6 September 2021 / Accepted: 10 September 2021 / Published: 22 September 2021
(This article belongs to the Special Issue Molecular Mechanisms of Tumor Development and Progression - A Themed Honorary Issue to Prof. Miguel Quintanilla)
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Abstract

The prognosis of advanced mesothelioma is poor. Podoplanin (PDPN) is highly expressed in most malignant mesothelioma. This study aimed to evaluate the potential alpha-radioimmunotherapy (RIT) with a newly developed anti-PDPN antibody, NZ-16, compared with a previous antibody, NZ-12. Methods: The in vitro properties of radiolabeled antibodies were evaluated by cell binding and competitive inhibition assays using PDPN-expressing H226 mesothelioma cells. The biodistribution of 111In-labeled antibodies was studied in tumor-bearing mice. The absorbed doses were estimated based on biodistribution data. Tumor volumes and body weights of mice treated with 90Y- and 225Ac-labeled NZ-16 were measured for 56 days. Histologic analysis was conducted. Results: The radiolabeled NZ-16 specifically bound to H226 cells with higher affinity than NZ-12. The biodistribution studies showed higher tumor uptake of radiolabeled NZ-16 compared with NZ-12, providing higher absorbed doses to tumors. RIT with 225Ac- and 90Y-labeled NZ-16 had a significantly higher antitumor effect than RIT with 90Y-labeled NZ-12. 225Ac-labeled NZ-16 induced a larger amount of necrotic change and showed a tendency to suppress tumor volumes and prolonged survival than 90Y-labeled NZ-16. There is no obvious adverse effect. Conclusions: Alpha-RIT with the newly developed NZ-16 is a promising therapeutic option for malignant mesothelioma.
Keywords: molecular radiotherapy; improved efficacy; tumor volume reduction; prolonged survival; actinium-225 molecular radiotherapy; improved efficacy; tumor volume reduction; prolonged survival; actinium-225
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MDPI and ACS Style

Sudo, H.; Tsuji, A.B.; Sugyo, A.; Kaneko, M.K.; Kato, Y.; Nagatsu, K.; Suzuki, H.; Higashi, T. Preclinical Evaluation of Podoplanin-Targeted Alpha-Radioimmunotherapy with the Novel Antibody NZ-16 for Malignant Mesothelioma. Cells 2021, 10, 2503. https://doi.org/10.3390/cells10102503

AMA Style

Sudo H, Tsuji AB, Sugyo A, Kaneko MK, Kato Y, Nagatsu K, Suzuki H, Higashi T. Preclinical Evaluation of Podoplanin-Targeted Alpha-Radioimmunotherapy with the Novel Antibody NZ-16 for Malignant Mesothelioma. Cells. 2021; 10(10):2503. https://doi.org/10.3390/cells10102503

Chicago/Turabian Style

Sudo, Hitomi, Atsushi B. Tsuji, Aya Sugyo, Mika K. Kaneko, Yukinari Kato, Kotaro Nagatsu, Hisashi Suzuki, and Tatsuya Higashi. 2021. "Preclinical Evaluation of Podoplanin-Targeted Alpha-Radioimmunotherapy with the Novel Antibody NZ-16 for Malignant Mesothelioma" Cells 10, no. 10: 2503. https://doi.org/10.3390/cells10102503

APA Style

Sudo, H., Tsuji, A. B., Sugyo, A., Kaneko, M. K., Kato, Y., Nagatsu, K., Suzuki, H., & Higashi, T. (2021). Preclinical Evaluation of Podoplanin-Targeted Alpha-Radioimmunotherapy with the Novel Antibody NZ-16 for Malignant Mesothelioma. Cells, 10(10), 2503. https://doi.org/10.3390/cells10102503

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