Journal Article Molecular imaging using an anti-human tissue factor monoclonal antibody in an orthotopic glioma xenograft model

Takashima, Hiroki  ,  Tsuji, Atsushi  ,  Saga, Tsuneo

Description
Nuclear medicine examinations for imaging gliomas have been introduced into clinical practice to evaluate the grade of malignancy and determine sampling locations for biopsies. However, these modalities have some limitations. Tissue factor (TF) is overexpressed in various types of cancers, including gliomas. We thus generated an anti-human TF monoclonal antibody (mAb) clone 1849. In the present study, immunohistochemistry performed on glioma specimens using anti-TF 1849 mAb showed that TF expression in gliomas increased in proportion to the grade of malignancy based on the World Health Organization (WHO) classification, and TF was remarkably expressed in necrosis and pseudopalisading cells, the histopathological hallmarks of glioblastoma multiforme (GBM). Furthermore, in both fluorescence and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging studies, anti-TF 1849 IgG efficiently accumulated in TF-overexpressing intracranial tumours in mice. Although further investigation is required for a future clinical use of immuno-SPECT with 111In-labelled anti-TF 1849 IgG, the immuno-SPECT may represent a unique imaging modality that can visualize the biological characteristics of gliomas differently from those obtained using the existing imaging modalities and may be useful to evaluate the grade of malignancy and determine sampling locations for biopsies in patients with glioma, particularly GBM.ContributionsY.M. provided the original concept for the research. H.T., M.Y. and Y.M. designed the study. H.T., A.B.T., Y.K. and J.K. performed the experiments. H.T., A.B.T., T.S., M.Y., Y.K., J.K., S.Y., J.K. and Y.M. discussed the results and wrote the manuscript.Competing InterestsThe authors declare that they have no competing interests.Corresponding authorCorrespondence to Yasuhiro Matsumura.CommentsBy submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.Creative Commons BYOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Article ToolsPDFShare on FacebookShare on TwitterTools sectionsfiguresreferencesAbstract Introduction Results Discussion Methods Additional information References Acknowledgements Author information Comments Nuclear medicine examinations for imaging gliomas have been introduced into clinical practice to evaluate the grade of malignancy and determine sampling locations for biopsies. However, these modalities have some limitations. Tissue factor (TF) is overexpressed in various types of cancers, including gliomas. We thus generated an anti-human TF monoclonal antibody (mAb) clone 1849. In the present study, immunohistochemistry performed on glioma specimens using anti-TF 1849 mAb showed that TF expression in gliomas increased in proportion to the grade of malignancy based on the World Health Organization (WHO) classification, and TF was remarkably expressed in necrosis and pseudopalisading cells, the histopathological hallmarks of glioblastoma multiforme (GBM). Furthermore, in both fluorescence and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging studies, anti-TF 1849 IgG efficiently accumulated in TF-overexpressing intracranial tumours in mice. Although further investigation is required for a future clinical use of immuno-SPECT with 111In-labelled anti-TF 1849 IgG, the immuno-SPECT may represent a unique imaging modality that can visualize the biological characteristics of gliomas differently from those obtained using the existing imaging

Number of accesses :  

Other information