Synthesis and characterization of cyanine dyes as contrast agents for near-infrared imaging

The diagnostic potential of the near-infrared imaging method can be enhanced using fluorescent dyes as contrast agents. In the pool of fluorescent dyes (e. g. tetrapyrroles, polymethines) the cyanine dyes are the most promising ones because of their high molar absorption between 700 and 1000 nm, minimal phototoxicity and convenient synthetic availability. The potential of Indocyanine Green (ICG) as a contrast agent for optical mammography has been investigated. The major drawbacks of this compound are a rapid liver uptake after intravenous injection, a low fluorescence quantum yield and low stability in aqueous solutions. Our purpose was to generate indotricarbocyanine derivatives structurally related to ICG with improved photophysical and pharmacological properties. Several dyes more hydrophilic than ICG and covering a wide polarity range were synthesized. The dyes were characterized photophysically (absorption and fluorescence spectra, molar absorptivities and fluorescence quantum yields in different physiological media) and physicochemically (partition coefficients, plasma protein binding).