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

Abstract

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.

• Authors: Hiroki Takashima, Atsushi B Tsuji, Tsuneo Saga, Masahiro Yasunaga, Yoshikatsu Koga, Jun-Ichiro Kuroda, Shigetoshi Yano, Jun-Ichi Kuratsu, Yasuhiro Matsumura
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 12341 (09 26 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28951589 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Immunoconjugates
• Indium Radioisotopes
• Thromboplastin
• Indium-111

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, immunology)
• Brain (diagnostic imaging, pathology)
• Brain Neoplasms (diagnostic imaging, pathology)
• Cell Line, Tumor
• Female
• Glioma (diagnostic imaging, pathology)
• Humans
• Immunoconjugates (administration & dosage, chemistry, immunology)
• Indium Radioisotopes (administration & dosage, chemistry)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Molecular Imaging (methods)
• Single Photon Emission Computed Tomography Computed Tomography
• Thromboplastin (immunology, metabolism)
• Xenograft Model Antitumor Assays