Synthesis and application of a water-soluble near-infrared dye for cancer detection using optical imaging.

A novel water-soluble 2-[2-(2-chloro-3-{2-[3,3-dimethyl-5-sulfo-1-(4-sulfo-butyl)-3H-indol-2-yl]-vinyl}-cyclohex-2-enylidene)-ethylidene]-3,3-dimethyl-1-(4-sulfo-butyl)-2,3-dihydro-1H-indole-5-carboxylic acid (dye 2) was developed via an asymmetric approach. With an additional sulfonate group, the near-infrared feature of this dye exhibited a 2-fold increase in quantum yield compared to the previous generation. The current synthetic strategy provided a single carboxylic group as a handle for conjugation, thus allowing selectivity for bioconjugation. The stability of this dye was demonstrated by labeling peptides via solid-phase peptide chemistry. The in vivo optical imaging showed potential and broad applications of this dye in developing molecular-based beacons for cancer detection.