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Shortwave Infrared (SWIR)-Emitting Tamoxifen-Conjugated Cyanine Dyes for Estrogen Receptor-Targeted Cancer Imaging
Aravind Kanda Swamy1, Mahadeva M M Swamy1,2, Kohei Yuyama3
1Graduate School of Life Science, Hokkaido University, Sapporo 001-0021, Japan.
Abstract:
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.
Insights
New imaging probes targeting estrogen receptors (ER) show promise for detecting ER-positive cancers. These probes utilize shortwave infrared (SWIR) fluorescence for deeper tumor visualization, aiding surgical resection.
Area of Science:
- Biomedical Imaging
- Organic Chemistry
- Oncology
Background:
- Fluorescence-guided surgery requires effective tumor-targeting agents for complete resection.
- Shortwave infrared (SWIR) imaging offers deeper tissue penetration than visible or near-infrared (NIR) imaging, reducing autofluorescence and scattering.
- Estrogen receptor (ER)-positive cancers are a significant clinical challenge.
Purpose of the Study:
- To develop novel ER-targeting imaging probes for SWIR fluorescence imaging.
- To evaluate the efficacy of these probes in visualizing ER-expressing cancer cells.
- To assess the potential of these probes for guiding surgical tumor resection.
Main Methods:
- Conjugation of tamoxifen (TAM), an ER-targeting ligand, with indocyanine green (ICG) to create ICG-TAM, ICG-C9-TAM, and ICG-C11-TAM.
- Evaluation of absorption and emission properties of the synthesized probes.
- Noninvasive SWIR fluorescence imaging in ER-expressing cervical and breast cancer cells.
Main Results:
- ICG-TAM, ICG-C9-TAM, and ICG-C11-TAM were successfully synthesized.
- ICG-TAM exhibits emission in both NIR and SWIR regions.
- ICG-C9-TAM and ICG-C11-TAM demonstrated effectiveness in SWIR fluorescence imaging of ER-positive cancer cells.
Conclusions:
- The developed TAM-ICG conjugates are effective SWIR imaging agents for ER-positive cancer cells.
- Receptor-targeted ligands can be utilized for specific biomolecular imaging in ER-positive cancer models.
- These probes hold potential for improving surgical outcomes in ER-positive cancers through enhanced visualization.
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