title: Development of anti-HER2 fragment antibody conjugated to iron oxide nanoparticles for in vivo HER2-targeted photoacoustic tumor imaging.
abstract: Photoacoustic (PA) imaging is a promising imaging modality that provides biomedical information with high sensitivity and resolution. Iron oxide nanoparticles (IONPs) have been regarded as remarkable PA contrast agents because of their low toxicity and biodegradable properties. However, IONP delivery is restricted by its modest leakage and retention in tumors. In this study, we designed IONPs (20nm, 50nm, and 100nm) conjugated with anti-HER2 moieties [whole IgG, single-chain fragment variable (scFv), and peptide] for HER2-targeted PA tumor imaging. The binding affinity, cellular uptake, and in vivo biodistribution were examined. We propose 20-nm anti-HER2 scFv-conjugated IONPs (SNP20) as a novel PA contrast agent. SNP20 demonstrated high affinity and specific binding to HER2-expressing cells; it selectively visualized HER2-positive tumors in PA imaging studies. These data indicate that SNP20 is a potential PA contrast agent for imaging of HER2-expressing tumors.
  
  
  BACKGROUND
  Iron oxide nanoparticles have been demonstrated to be good contrast agents for tumor imaging. They may also be useful in photoacoustic (PA) imaging, which can provide high sensitivity data and image resolution. The authors here coupled iron oxide nanoparticles with anti-HER2 antibody fragment and showed significant retention of these nanoparticles in tumors. This combination may provide another option for enhanced imaging of tumors.
authors.affiliation: Medical Imaging Project, Corporate R&D Headquarters, Canon Inc., Ohta-ku, Tokyo, Japan; Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kanazaki
authors.affiliation: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan; Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Sano
authors.affiliation: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan; Biomedical Imaging Research Center, University of Fukui, Eiheiji-cho, Yoshida-gun, Fukui, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Makino
authors.affiliation: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Medical Imaging Project, Corporate R&D Headquarters, Canon Inc., Ohta-ku, Tokyo, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Yamauchi
authors.affiliation: Medical Imaging Project, Corporate R&D Headquarters, Canon Inc., Ohta-ku, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Ning
authors.initials: N
authors.lastname: Ding
authors.affiliation: Medical Imaging Project, Corporate R&D Headquarters, Canon Inc., Ohta-ku, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yano
authors.affiliation: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan; Department of Investigative Radiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Temma
authors.affiliation: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan. Electronic address: hsaji@pharm.kyoto-u.ac.jp.
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000493:pharmacokinetics; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis*; D061088:Photoacoustic Techniques / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D018796:Immunoconjugates; D018719:Erb-b2 Receptor Tyrosine Kinases; D057127:Single-Chain Antibodies; C000499:ferric oxide
keywords: HER2; Iron oxide nanoparticle; Photoacoustic imaging; Single-chain Fv