Open AccessMinibody-Indocyanine Green Based Activatable Optical Imaging Probes: The Role of Short Polyethylene Glycol Linkers
Author(s) -
Rira Watanabe,
Kazuhide Sato,
Hirofumi Hanaoka,
Toshiko Harada,
Takahito Nakajima,
Insook Kim,
Chang H. Paik,
Anna M. Wu,
Peter L. Choyke,
Hisataka Kobayashi
Publication year - 2014
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml400533y
Subject(s) - indocyanine green , fluorophore , biodistribution , polyethylene glycol , conjugated system , peg ratio , fluorescence , covalent bond , fluorescence lifetime imaging microscopy , in vivo , molecular imaging , chemistry , biophysics , materials science , medicine , pathology , polymer , in vitro , biochemistry , organic chemistry , optics , physics , microbiology and biotechnology , finance , economics , biology
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.