title: In vivo assessment of HER2 receptor density in HER2-positive tumors by near-infrared imaging, using repeated injections of the fluorescent probe.
abstract: HER2 overexpression and amplification of the HER2/neu gene have been found in approximately 25% of invasive breast carcinomas. They are associated with a poor prognosis and resistance to therapy in breast cancer patients. Up to now, clinical evaluation of human epidermal growth factor receptor 2 (HER2) expression is based on ex vivo methods (immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) staining of biopsied tissue). Our goal is to realize "image and treat" paradigm using targeted fluorescent probes to evaluate expression levels of cell biomarkers responsible for cancer progression and to monitor the efficacy of corresponding monoclonal antibody treatments. We used fluorescent Affibody-based probes for in vivo analysis of HER2 receptors using near-infrared optical imaging that do not interfere with binding of the therapeutic agents to these receptors. We have analyzed two types of breast carcinoma xenografts with significant differences in HER2 expression (31 and 21 according to classification) in the mouse model. Using our kinetic model to analyze the temporal variations of the fluorescence intensity in the tumor area after two subsequent injections allowed us to assess quantitatively the difference in HER2 expression levels for two tumor types (BT-474 and MD-MBA-361). This result was substantiated by ELISA ex vivo assays of HER2 expression in the same tumors.
authors.affiliation: NIH/National Institute of Child Health and Human Development, Building 9, 9 Memorial Drive, Bethesda, MD 20892. gandjbaa@mail.nih.gov.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Ardeshirpour
authors.forename: Moinuddin
authors.initials: M
authors.lastname: Hassan
authors.forename: Rafal
authors.initials: R
authors.lastname: Zielinski
authors.forename: Jason  A
authors.initials: J
authors.lastname: Horton
authors.forename: Jacek
authors.initials: J
authors.lastname: Capala
authors.forename: Amir H
authors.initials: AH
authors.lastname: Gandjbakhche
authors.forename: Victor
authors.initials: V
authors.lastname: Chernomordik
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage; D006801:Humans; D007275:Injections, Intravenous; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D019265:Spectroscopy, Near-Infrared
chemical_list: D005456:Fluorescent Dyes; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human