title: Minibody-indocyanine green based activatable optical imaging probes: the role of short polyethylene glycol linkers.
abstract: Minibodies show rapider blood clearance than IgGs due to smaller size that improves target-to-background ratio (TBR) in in vivo imaging. Additionally, the ability to activate an optical probe after binding to the target greatly improves the TBR. An optical imaging probe based on a minibody against prostate-specific membrane antigen (PSMA-MB) and conjugated with an activatable fluorophore, indocyanine green (ICG), was designed to fluoresce only after binding to cell-surface PSMA. To further reduce background signal, short polyethylene glycol (PEG) linkers were employed to improve the covalent bonding ratio of ICG. New PSMA-MBs conjugated with bifunctional ICG derivatives specifically visualized PSMA-positive tumor xenografts in mice bearing both PSMA-positive and -negative tumors within 6 h postinjection. The addition of short PEG linkers significantly improved TBRs; however, it did not significantly alter the biodistribution. Thus, minibody-ICG conjugates could be a good alternative to IgG-ICG in the optical cancer imaging for further clinical applications.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Rira
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Sato
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hanaoka
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Harada
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Takahito
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory , Frederick, Maryland 21702, United States.
authors.forename: Insook
authors.initials: I
authors.lastname: Kim
authors.affiliation: Nuclear Medicine Department, Radiology and Imaging Science, Warren Grant Magnuson Clinical Center, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Chang H
authors.initials: CH
authors.lastname: Paik
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA , Los Angeles, California 90095, United States.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wu
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
keywords: Molecular imaging; indocyanine green; minibody; near-infrared fluorescence; prostate cancer