Targeted zwitterionic near-infrared fluorophores for improved optical imaging
Top Cited Papers
- 6 January 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Biotechnology
- Vol. 31 (2), 148-153
- https://doi.org/10.1038/nbt.2468
Abstract
Diagnostic and surgical procedures that rely on optical imaging are improved by using near-infrared fluorescent probes with low background signal. The signal-to-background ratio (SBR) is the key determinant of sensitivity, detectability and linearity in optical imaging. As signal strength is often constrained by fundamental limits, background reduction becomes an important approach for improving the SBR. We recently reported that a zwitterionic near-infrared (NIR) fluorophore, ZW800-1, exhibits low background. Here we show that this fluorophore provides a much-improved SBR when targeted to cancer cells or proteins by conjugation with a cyclic RGD peptide, fibrinogen or antibodies. ZW800-1 outperforms the commercially available NIR fluorophores IRDye800-CW and Cy5.5 in vitro for immunocytometry, histopathology and immunoblotting and in vivo for image-guided surgery. In tumor model systems, a tumor-to-background ratio of 17.2 is achieved at 4 h after injection of ZW800-1 conjugated to cRGD compared to ratios of 5.1 with IRDye800-CW and 2.7 with Cy5.5. Our results suggest that introducing zwitterionic properties into targeted fluorophores may be a general strategy for improving the SBR in diagnostic and therapeutic applications.Keywords
This publication has 35 references indexed in Scilit:
- Synthesis and In Vivo Fate of Zwitterionic Near‐Infrared FluorophoresAngewandte Chemie, 2011
- Rapid translocation of nanoparticles from the lung airspaces to the bodyNature Biotechnology, 2010
- Programmable in situ amplification for multiplexed imaging of mRNA expressionNature Biotechnology, 2010
- The use of fluorescent dyes and probes in surgical oncologyEuropean Journal of Surgical Oncology, 2010
- New Strategies for Fluorescent Probe Design in Medical Diagnostic ImagingChemical Reviews, 2009
- Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probesNature Medicine, 2008
- Real-time intraoperative assessment of the extrahepatic bile ducts in rats and pigs using invisible near-infrared fluorescent lightSurgery, 2008
- Renal clearance of quantum dotsNature Biotechnology, 2007
- Radiolabeled and near-infrared fluorescent fibrinogen derivatives create a system for the identification and repair of obscure gastrointestinal bleedingSurgery, 2006
- An HPLC/mass spectrometry platform for the development of multimodality contrast agents and targeted therapeutics: prostate‐specific membrane antigen small molecule derivativesContrast Media & Molecular Imaging, 2006