ABSTRACT
BACKGROUND: Insulin-like growth factor-binding protein 7 (IGFBP7) is an abundant, selective and accessible biomarker of glioblastoma multiforme (GBM) tumour vessels. In this study, an anti-IGFBP7 single-domain antibody (sdAb) was developed to target GBM vessels for molecular imaging applications. METHODS: Human GBM was modelled in mice by intracranial implantation of U87MG.EGFRvIII cells. An anti-IGFBP7 sdAb, isolated from an immune llama library by panning, was assessed in vitro for its binding affinity using surface plasmon resonance and by ex vivo immunobinding on mouse and human GBM tissue. Tumour targeting by Cy5.5-labelled anti-IGFBP7 sdAb as well as by anti-IGFBP7 sdAb conjugated to PEGylated Fe3O4 nanoparticles (NPs)-Cy5.5 were assessed in U87MG.EGFRvIII tumour-bearing mice in vivo using optical imaging and in brain sections using fluorescent microscopy. RESULTS: Surface plasmon resonance analyses revealed a medium affinity (K(D)=40-50 nM) binding of the anti-IGFBP7 sdAb to the purified antigen. The anti-IGFBP7 sdAb also selectively bound to both mouse and human GBM vessels, but not normal brain vessels in tissue sections. In vivo, intravenously injected anti-IGFBP7 sdAb-Cy5.5 bound to GBM vessels creating high imaging signal in the intracranial tumour. Similarly, the anti-IGFBP7 sdAb-functionalised PEGylated Fe3O4 NP-Cy5.5 demonstrated enhanced tumour signal compared with non-targeted NPs. Fluorescent microscopy confirmed the presence of anti-IGFBP7 sdAb and anti-IGFBP7 sdAb-PEGylated Fe3O4 NPs selectively in GBM vessels. CONCLUSIONS: Anti-IGFBP7 sdAbs are novel GBM vessel-targeting moieties suitable for molecular imaging.
Subject(s)
Brain Neoplasms/pathology , Glioblastoma/pathology , Insulin-Like Growth Factor Binding Proteins/immunology , Animals , Antibodies , Brain/immunology , Brain/pathology , Brain Neoplasms/immunology , Brain Neoplasms/ultrastructure , DNA Primers , DNA, Complementary/genetics , DNA, Complementary/immunology , Gene Amplification , Glioblastoma/immunology , Glioblastoma/ultrastructure , Humans , Immunoglobulin G/immunology , Immunohistochemistry , Insulin-Like Growth Factor Binding Proteins/metabolism , Mice , Microscopy, Fluorescence , Polymerase Chain Reaction , Tissue DistributionABSTRACT
PURPOSE: To report a 61-year-old man with sudden onset of visual loss in both eyes related to bilateral macular ischemia. METHODS: The patient underwent comprehensive ophthalmic examination including slit-lamp and fundus examination, fluorescein angiography, and visual field testing as well as biologic screening. RESULTS: Bilateral macular ischemia associated with peripheral retinal vasculitis was confirmed by angiography. We diagnosed Behçet disease by association of ocular, oral, and cutaneous involvement according to the criteria of the international study group for Behçet disease. The patient was treated with corticosteroids. CONCLUSION: In Behçet disease, sudden onset of bilateral vision loss may be associated with bilateral retinal vascular disease and macular ischemia. Prompt diagnosis and treatment with systemic corticosteroids may be beneficial.
Subject(s)
Behcet Syndrome/complications , Ischemia/etiology , Macula Lutea/blood supply , Vision Disorders/etiology , Behcet Syndrome/diagnosis , Behcet Syndrome/immunology , Fluorescein Angiography , Follow-Up Studies , Fundus Oculi , Glucocorticoids/therapeutic use , HLA-B Antigens/immunology , HLA-B51 Antigen , Histocompatibility Testing , Humans , Ischemia/diagnosis , Ischemia/drug therapy , Male , Middle Aged , Vision Disorders/diagnosis , Vision Disorders/drug therapy , Visual Acuity , Visual FieldsABSTRACT
We reported on the case of a seven years-old boy suffering from an acute unilateral proptosis. Diagnosis of orbital lymphangioma was made with Magnetic Resonance Imaging (MRI) showing an intra-tumoral hemorrhage in a vascular tumor unrelated to general circulation. Authors underlined the interest of MRI due to its unique ability to characterize hemorrhage with hemodynamic isolation and to plan therapeutic approach. Even controversial, conservative management remained the best choice but surgery should be considered if vision is threatened.
Subject(s)
Lymphangioma/diagnosis , Orbital Neoplasms/diagnosis , Child , Humans , Lymphangioma/diagnostic imaging , Lymphangioma/therapy , Magnetic Resonance Imaging , Male , Orbital Neoplasms/diagnostic imaging , Orbital Neoplasms/therapy , RadiographyABSTRACT
Inflammatory exophthalmos with visual loss due to optic atrophy is reported in a 45-year-old man. Computed tomography showed an ethmoido-frontal mucocel. This single case stresses the severe complication of a mucocel like optic nerve head atrophy. The different tools for diagnosis and treatment are also emphasized.
