title: Quantitative analysis of Her2 receptor expression in vivo by near-infrared optical imaging.
abstract: Human epidermal growth factor receptor 2 (HER2) overexpression in breast cancers is associated with poor prognosis and resistance to therapy. Current techniques for estimating this important characteristic use ex vivo assays that require tissue biopsies. We suggest a novel noninvasive method to characterize HER2 expression in vivo, using optical imaging, based on HER2-specific probes (albumin-binding domain-fused-(ZHER2:342)2-Cys Affibody molecules [Affibody AB, Solna, Sweden], labeled with Alexa Fluor 750 [Molecular Probes, Invitrogen, Carlsbad, CA]) that could be used concomitantly with HER2-targeted therapy. Subcutaneous tumor xenografts, expressing different levels of HER2, were imaged with a near-infrared fluorescence small-animal imaging system at several times postinjection of the probe. The compartmental ligand-receptor model was used to calculate HER2 expression from imaging data. Correlation between HER2 amplification/overexpression in tumor cells and parameters, directly estimated from the sequence of optical images, was observed (eg, experimental data for BT474 xenografts indicate that initial slope, characterizing the temporal dependence of the fluorescence intensity detected in the tumor, linearly depends on the HER2 expression, as measured ex vivo by an enzyme-linked immunosorbent assay for the same tumor). The results obtained from tumors expressing different levels of HER2 substantiate a similar relationship between the initial slope and HER2 amplification/overexpression. This work shows that optical imaging, combined with mathematical modeling, allows noninvasive monitoring of HER2 expression in vivo.
authors.affiliation: Program on Pediatric Imaging and Tissue Sciences, Section on Analytical and Functional Biophotonics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Chernomordik
authors.forename: Moinuddin
authors.initials: M
authors.lastname: Hassan
authors.forename: Sang Bong
authors.initials: SB
authors.lastname: Lee
authors.forename: Rafal
authors.initials: R
authors.lastname: Zielinski
authors.forename: Amir
authors.initials: A
authors.lastname: Gandjbakhche
authors.forename: Jacek
authors.initials: J
authors.lastname: Capala
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D015870:Gene Expression; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013388:Succinimides / Q000493:pharmacokinetics; D014183:Transplantation, Heterologous
chemical_list: D005456:Fluorescent Dyes; D018796:Immunoconjugates; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D013388:Succinimides; C502599:Alexa Fluor 750; C508053:ERBB2 protein, human