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Anti-GD2 antibody for radiopharmaceutical imaging of osteosarcoma

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

Abstract

Purpose

Osteosarcoma (OS) is the most frequently diagnosed bone cancer in children with little improvement in overall survival in the past decades. The high surface expression of disialoganglioside GD2 on OS tumors and restricted expression in normal tissues makes it an ideal target for anti-OS radiopharmaceuticals. Since human and canine OS share many biological and molecular features, spontaneously occurring OS in canines has been an ideal model for testing new imaging and treatment modalities for human translation. In this study, we evaluated a humanized anti-GD2 antibody, hu3F8, as a potential delivery vector for targeted radiopharmaceutical imaging of human and canine OS.

Methods

The cross-reactivity of hu3F8 with human and canine OS cells and tumors was examined by immunohistochemistry and flow cytometry. The hu3F8 was radiolabeled with indium-111, and the biodistribution of [111In]In-hu3F8 was assessed in tumor xenograft-bearing mice. The targeting ability of [111In]In-hu3F8 to metastatic OS was tested in spontaneous OS canines.

Results

The hu3F8 cross reacts with human and canine OS cells and canine OS tumors with high binding affinity. Biodistribution studies revealed selective uptake of [111In]In-hu3F8 in tumor tissue. SPECT/CT imaging of spontaneous OS canines demonstrated avid uptake of [111In]In-hu3F8 in all metastatic lesions. Immunohistochemistry confirmed the extensive binding of radiolabeled hu3F8 within both osseous and soft lesions.

Conclusion

This study demonstrates the feasibility of targeting GD2 on OS cells and spontaneous OS canine tumors using hu3F8-based radiopharmaceutical imaging. Its ability to deliver an imaging payload in a targeted manner supports the utility of hu3F8 for precision imaging of OS and potential future use in radiopharmaceutical therapy.

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Data availability

All data associated with this study are present in the paper or the Supplementary Materials.

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Funding

This work was supported by the National Institutes Health grants: R01 CA116477, R01 CA187037, and R01 CA239124.

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Author notes

  1. Yingli Fu, Jing Yu and Ioanna Liatsou contributed equally.

Authors and Affiliations

  1. Department of Radiology and Radiological Science, the Johns Hopkins University School of Medicine, MD, Baltimore, USA

    Yingli Fu, Jing Yu, Ioanna Liatsou, Yong Du, Anders Josefsson, Jessie R. Nedrow, Dara L. Kraitchman & George Sgouros

  2. Department of Veterinary Medicine & Surgery, the University of Missouri, Columbia, MO, USA

    Hans Rindt & Jeffrey N. Bryan

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  1. Yingli Fu
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Contributions

Y. F., J. Y., and I. L. designed and performed all the murine experiments and collected and analyzed the data. Y. F. and J. Y. wrote the original manuscript, and all authors reviewed and edited the manuscript.

Y. D., A. J., and J. N. collected, analyzed, and interpreted data from SPECT/CT images.

H. R. and J. B. collected and analyzed flow cytometry data.

D. L. K. and G. S. acquired funding, directed the research, and supervised in the design and interpretation of the experiments and the writing of the manuscript.

D. L. K. performed all the canine experiments.

Corresponding author

Correspondence to George Sgouros.

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Ethics approval and consent to participate

Animal protocols were approved by the Animal Care and Use Committee of the Johns Hopkins University, School of Medicine. Client-owned dogs with confirmed metastatic OS were recruited from owners with written informed consent.

Conflict of interest

The authors report no relevant conflicts of interest.

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Fu, Y., Yu, J., Liatsou, I. et al. Anti-GD2 antibody for radiopharmaceutical imaging of osteosarcoma. Eur J Nucl Med Mol Imaging 49, 4382–4393 (2022). https://doi.org/10.1007/s00259-022-05888-5

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  • DOI: https://doi.org/10.1007/s00259-022-05888-5

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