Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 5, Issue 4, Pages 411-415Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ml400533y
Keywords
Molecular imaging; minibody; indocyanine green; prostate cancer; near-infrared fluorescence
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Funding
- Intramural Research Program of the NCI/NIH
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
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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.
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