In vivo imaging of brain cancer using epidermal growth factor single domain antibody bioconjugated to near-infrared quantum dots.
Diagnosis of glioblastoma multiform (GBM) with MRI lacks molecular information and requires a biopsy for pathologic confirmation. The EGFRvIII, is a constitutively active mutant of the EGF receptor, identified in a high percentage of brain cancers and associated with increased invasiveness and resistance, making it a good target to improve imaging and diagnosis. The present study shows that conjugation of near-infrared quantum dot (Qd800) to an anti-EGFRvIII single domain antibody, made of the variable region with an extra cysteine for site-specific conjugation (EG2-Cys), increased its internalization in U87MG-EGFRvIII cells in vitro compared to Qd800 conjugated with the Fc region of the antibody (EG2-hFc) or unconjugated. EG2-Cys also improved the contrast in Near-Infrared Imaging of mice bearing orthotopic glioblastoma. The increased accumulation was confirmed by fluorescence microscopy of brain sections. The specificity of EG2-Cys in brain tumor expressing the EGFRvIII mutant receptor may provide an accurate less invasive diagnosis and determine the level of tumor aggressiveness and resistance.
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Abulrob
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D007259:Infrared Rays; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods; D057054:Molecular Imaging / Q000379:methods*; D045663:Quantum Dots; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; C541485:EGFR protein, mouse; D066246:ErbB Receptors