Preparation of alkyne-labeled 2-nitroimidazoles for identification of tumor hypoxia by Raman spectroscopy.

Hypoxia is a characteristic feature of solid tumors. Herein, we have developed novel hypoxia-sensitive probes (IM-ACs) for Raman spectroscopic analysis, consisting of nitroimidazole as a hypoxia-targeting unit and acetylene group as the signal-emitting unit. Among IM-ACs synthesized in this study, IM-AC possessing a diacetylene group (IM-AC 3), showed suitable properties as a hypoxia indicator. When administered to A549 cells, we observed a strong signal of IM-AC 3 around 2200cm(-1) in the Raman spectra from hypoxic cells. Ex vivo experiments suggest that IM-AC 3 remained in hypoxic tumor tissue and emitted a strong signal.