Indocyanine Blue (ICB) as a Functional Alternative to Indocyanine Green (ICG) for Enhanced 700 nm NIR Imaging

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Despite significant advancements in bioimaging technology, only a limited number of fluorophores are currently approved for clinical applications. Indocyanine green (ICG) is the first FDA-approved near-infrared (NIR) fluorophore and has significantly advanced clinical interventions over the past three decades. However, its single-channel imaging at 800 nm emission is often insufficient for capturing comprehensive diagnostic information during surgery. In this study, we evaluate indocyanine blue (ICB), an ICG analog with a shorter polymethine bridge, as a promising candidate for multi-channel NIR imaging. ICB demonstrated peak absorption and emission approximately 100 nm shorter than ICG in aqueous solutions, placing it within the 700 nm range of the NIR window. Furthermore, ICB exhibited favorable solubility and optical properties in aqueous environments, supporting its potential for in vivo imaging applications. Notably, ICB shows rapid systemic clearance, likely due to its lower molecular weight, which facilitates clear visualization in angiography, cholangiography, and lymph node mapping with minimal background interference. Additionally, dual-channel imaging of tumors and lymph nodes was achieved using a tumor-targeting fluorophore in conjunction with ICB, illustrating the potential for enhanced intraoperative guidance. ICB emitting at 700 nm, therefore, can be useful in NIR imaging, broadening the possibilities for improved diagnostic accuracy and therapeutic outcomes in clinical settings.