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Fluorescence Molecular Tomography for In Vivo Imaging of Glioblastoma Xenografts
Published on: April 26, 2018
Molecular imaging using an anti-human tissue factor monoclonal antibody in an orthotopic glioma xenograft model
Hiroki Takashima1,2, Atsushi B Tsuji3, Tsuneo Saga3
1Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
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.
Insights
A new antibody targeting tissue factor (TF) shows promise for glioma imaging. This antibody accurately reflects tumor malignancy and aids in biopsy guidance, potentially improving glioma diagnosis and treatment strategies.
Area of Science:
- Oncology
- Immunology
- Medical Imaging
Background:
- Nuclear medicine imaging is used for glioma grading and biopsy guidance but has limitations.
- Tissue factor (TF) is overexpressed in gliomas and correlates with malignancy.
- Existing imaging modalities do not fully capture glioma's biological characteristics.
Purpose of the Study:
- To develop and evaluate an anti-TF monoclonal antibody (mAb) clone 1849 for glioma imaging.
- To assess the correlation between TF expression and glioma grade.
- To explore the potential of TF-targeted immuno-SPECT for glioma diagnosis.
Main Methods:
- Immunohistochemistry using anti-TF 1849 mAb on glioma specimens.
- Fluorescence and SPECT/CT imaging studies in mice with intracranial tumors.
- In vitro and in vivo characterization of anti-TF 1849 IgG accumulation.
Main Results:
- TF expression in gliomas increased with World Health Organization (WHO) malignancy grade.
- TF was highly expressed in necrosis and pseudopalisading cells, characteristic of glioblastoma multiforme (GBM).
- Anti-TF 1849 IgG demonstrated efficient accumulation in TF-overexpressing intracranial tumors in vivo.
Conclusions:
- Anti-TF 1849 mAb is a potential biomarker for glioma malignancy grading.
- Immuno-SPECT with 111In-labelled anti-TF 1849 IgG may offer a novel imaging approach for gliomas.
- This modality could improve biopsy site selection and assessment of glioma biological features, especially for GBM.
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