Impact of Substituents in Tumor Uptake and Fluorescence Imaging Ability of Near-Infrared Cyanine-like Dyes.

ABSTRACT

This report presents a simple strategy to introduce various functionalities in a cyanine dye (bis-indole-N-butylsulfonate-polymethine bearing a fused cyclic chloro-cyclohexene ring structure), and assess the impact of these substitutions in tumor uptake, retention and imaging. The results obtained from the structural activity relationship (SAR) study demonstrate that certain structural features introduced in the cyanine dye moiety make a remarkable difference in tumor avidity. Among the compounds investigated, the symmetrical CDs containing an amino-phenyl thioether group attached to a cyclohexene ring system and the two N-butyl linkers with terminal sulfonate groups in benzoindole moieties exhibited excellent tumor imaging ability in BALB/c mice bearing Colon26 tumors. Compared to indocyanine green (ICG), approved by FDA as a blood pooling agent, which has also been investigated for the use in tumor imaging, the modified CD selected on the basis of SAR study produced enhanced uptake and longer retention in tumor(s). A facile approach reported herein for introducing a variety of functionalities in tumor-avid CD provides an opportunity to create multi-imaging modality agent(s). Using a combination of mass spectrometry and absorbance techniques, the photobleaching of one of the CDs was analyzed and significant regioselective photooxidation was observed.