An Estrogen Receptor α-Targeted NIR-II Probe for Breast Tumor Imaging and Image-Guided Surgery

Area of Science:

• Oncology
• Medical Imaging
• Biochemistry

Background:

• Breast cancer (BC) poses a significant global health challenge, with estrogen receptor α (ERα)-positive (ERα+) subtypes accounting for approximately 70% of cases.
• ERα plays a crucial role in the development and spread of ERα+ BC, making it a key target for diagnostic and therapeutic strategies (theranostics).

Purpose of the Study:

• To develop and assess a novel ERα-targeted fluorescent probe, IRDye800-4OHT, for enhanced detection and imaging of ERα-positive breast cancer.
• To evaluate the probe's specificity, binding affinity, biocompatibility, and efficacy in both in vitro and in vivo models.

Main Methods:

• Conjugation of the ERα-targeting ligand 4-hydroxytamoxifen with the near-infrared fluorescence dye IRDye800CW to create the IRDye800-4OHT probe.
• Assessment of the probe's spectral properties, binding affinity (RBA), and biocompatibility.
• In vitro cellular uptake studies to confirm ERα targeting specificity.
• In vivo near-infrared-II (NIR-II) imaging in animal models to visualize ERα expression in tumors and guide surgical resection.

Main Results:

• The IRDye800-4OHT probe exhibited second near-infrared (NIR-II) imaging capabilities (λem = 950 nm) and a high binding affinity (RBA = 2.3) for ERα.
• In vitro studies confirmed the probe's specific uptake by ERα-expressing cells.
• In vivo NIR-II imaging demonstrated real-time visualization of ERα in tumors, accurate tumor delineation, and successful guidance of breast tumor resection.

Conclusions:

• IRDye800-4OHT serves as a highly effective tool for the precise diagnosis of ERα-positive breast cancer.
• The probe facilitates real-time imaging and can guide surgical excision, potentially improving patient outcomes for ERα+ BC.
• This targeted fluorescent probe shows promise for advancing theranostic applications in ERα-positive breast cancer management.