title: AG73-modified Bubble liposomes for targeted ultrasound imaging of tumor neovasculature.
abstract: Ultrasound imaging is a widely used imaging technique. The use of contrast agents has become an indispensible part of clinical ultrasound imaging, and molecular imaging via ultrasound has recently attracted significant attention. We recently reported that "Bubble liposomes" (BLs) encapsulating US imaging gas liposomes were suitable for ultrasound imaging and gene delivery. The 12 amino acid AG73 peptide derived from the laminin α1 chain is a ligand for syndecans, and syndecan-2 is highly expressed in blood vessels. In this study, we prepared AG73 peptide-modified BLs (AG73-BLs) and assessed their specific attachment and ultrasound imaging ability for blood vessels in vitro and in vivo. First, we assessed the specific attachment of AG73-BLs in vitro, using flow cytometry and microscopy. AG73-BLs showed specific attachment compared with non-labeled or control peptide-modified BLs. Next, we examined ultrasound imaging in tumor-bearing mice. When BLs were administered, contrast imaging of AG73-BLs was sustainable for up to 4 min, while contrast imaging of non-labeled BLs was not observed. Thus, it is suggested that AG73-BLs may become useful ultrasound contrast agents in the clinic for diagnosis based on ultrasound imaging.
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan. negishi@toyaku.ac.jp
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Negishi
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Hamano
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tsunoda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oda
authors.forename: Batsuren
authors.initials: B
authors.lastname: Choijamts
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo-Takahashi
authors.forename: Daiki
authors.initials: D
authors.lastname: Omata
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Nomizu
authors.forename: Makoto
authors.initials: M
authors.lastname: Emoto
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Aramaki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007797:Laminin / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D045423:Microbubbles; D009369:Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D053669:Syndecan-2 / Q000378:metabolism; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D007797:Laminin; D008081:Liposomes; D009842:Oligopeptides; D053669:Syndecan-2; C084098:laminin A