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: Rira Watanabe, Kazuhide Sato, Hirofumi Hanaoka, Toshiko Harada, Takahito Nakajima, Insook Kim, Chang H Paik, Anna M Wu, Peter L Choyke, Hisataka Kobayashi
• Journal: ACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 5 Issue 4 Pg. 411-5 (Apr 10 2014) ISSN: 1948-5875 [Print] United States
• PMID: 24900850 (Publication Type: Journal Article)