Shortwave Infrared (SWIR)-Emitting Tamoxifen-Conjugated Cyanine Dyes for Estrogen Receptor-Targeted Cancer Imaging

Fluorescence-guided tumor detection using tumor-targeting imaging agents is critical for achieving complete surgical resection with tumor-free margins. Shortwave infrared (SWIR, 900-1400 nm) fluorescence imaging enables deeper tissue penetration due to reduced tissue autofluorescence and scattering relative to conventional visible (400-700 nm) and near-infrared (NIR, 700-900 nm) imaging. In this study, a series of estrogen receptor (ER)-targeting imaging probes were developed by conjugating the anticancer drug-based ligand tamoxifen (TAM) with the FDA-approved indocyanine green (ICG), yielding ICG-TAM and its π-conjugated extended analogues, ICG-C9-TAM and ICG-C11-TAM. Although ICG-TAM exhibits peak absorption and emission in the NIR region, it also emits in the SWIR region. ICG-C9-TAM and ICG-C11-TAM were further evaluated for noninvasive SWIR fluorescence imaging. SWIR fluorescence imaging was performed in ER-expressing cervical and breast cancer cells using the TAM conjugates. These findings support the use of receptor-targeted ligands for specific biomolecular imaging in ER-positive cancer models.