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700-nm Zwitterionic Near-Infrared Fluorophores for Dual-Channel Image-Guided Surgery
Hyun, H.,Henary, M.,Gao, T.,Narayana, L.,Owens, E. A.,Lee, J. H.,Park, G.,Wada, H.,Ashitate, Y.,Frangioni, J. V. Elsevier Science B.V., Amsterdam. 2016 Molecular imaging and biology Vol.18 No.1
<P>Purpose: The purpose of this study was to develop a family of 700-nm zwitterionic pentamethine indocyanine near-infrared fluorophores that would permit dual-channel image-guided surgery. Procedures: Three complementary synthetic schemes were used to produce novel zwitterionic chemical structures. Physicochemical, optical, biodistribution, and clearance properties were compared to Cy5.5, a conventional pentamethine indocyanine now used for biomedical imaging. Results: ZW700-1a, ZW700-1b, and ZW700-1c were synthesized, purified, and analyzed extensively in vitro and in vivo. All molecules had extinction coefficients >= 199,000 M-1 cm(-1), emission >= 660 nm, and stability >= 99 % after 24 h in warm serum. In mice, rats, and pigs, >= 80 % of the injected dose was completely eliminated from the body via renal clearance within 4 h. Either alone or conjugated to a tumor targeting ligand, ZW700-1a permitted dual-channel, high SBR, and simultaneous imaging with 800-nm NIR fluorophores using the FLARE (R) imaging system. Conclusions: Novel 700-nm zwitterionic NIR fluorophores enable dual-NIR image-guided surgery.</P>