title: Comparison of visible and near-infrared wavelength-excitable fluorescent dyes for molecular imaging of cancer.
abstract: Targeted fluorescent molecular imaging probes may provide an optimal means of detecting disease. Stable, organic fluorophores can be repeatedly excited in vivo by propagated light and consequentially can provide large signal-to-noise ratios (SNRs) for image detection of target tissues. In the literature, many small animal imaging studies are performed with a red excitable dye, Cy5.5, conjugated to the targeting component. We report the comparison of the in vivo fluorescent imaging performance of a near-IR (NIR) and a red-excitable dye. Epidermal growth factor (EGF) was conjugated with Cy5.5 [excitation/emission (ex/em), 660710 nm] or IRDye 800CW (ex/em: 785830 nm) for imaging EGF receptor (EGFr) positive (MDA-MB-468) and/or negative (MDA-MB-435) human breast cancer cell lines in subcutaneous xenograft models. The conjugates were injected intravenously at 1-nmol-dye equivalent with and without anti-EGFr monoclonal antibody C225, preadministered 24 h prior as a competitive ligand to EGFr. Our images show that while both agents target EGFr, the EGF-IRDye 800CW evidenced a significantly reduced background and enhanced the tumor-to-background ratio (TBR) compared to the EGF-Cy5.5. Immunohistochemistry shows that EGF causes activation of the EGFr signaling pathway, suggesting that prior to use as a targeting, diagnostic agent, potential deleterious effects should be considered.
authors.affiliation: Baylor College of Medicine, Department of Radiology, One Baylor Plaza, MS 360, Houston, Texas 77030, USA.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Adams
authors.forename: Shi
authors.initials: S
authors.lastname: Ke
authors.forename: Sunkuk
authors.initials: S
authors.lastname: Kwon
authors.forename: Feng
authors.initials: F
authors.lastname: Liang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Fan
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Karen
authors.initials: K
authors.lastname: Hirschi
authors.forename: Michel E
authors.initials: ME
authors.lastname: Mawad
authors.forename: Michael A
authors.initials: MA
authors.lastname: Barry
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002232:Carbocyanines; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007211:Indoles; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013055:Spectrophotometry, Infrared / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; C427728:IRDye800; D007211:Indoles; D004815:Epidermal Growth Factor