A zwitterionic near-infrared dye linked TrkC targeting agent for imaging metastatic breast cancer

Area of Science:

• Oncology
• Medical Imaging
• Bioconjugate Chemistry

Background:

• Targeted agents for cancer imaging and chemotherapy face unmet needs.
• Previous TrkC targeting agents for breast cancer had limitations in optical imaging.
• TrkC receptor is a potential target for metastatic breast cancer diagnosis and treatment.

Purpose of the Study:

• To develop a novel near-infrared (NIR) fluorescent probe for in vivo imaging of TrkC-positive metastatic breast tumors.
• To evaluate the targeting specificity and efficacy of the developed NIR probe in a preclinical model.
• To address limitations in optical imaging for metastatic breast cancer detection.

Main Methods:

• Conjugation of a TrkC targeting fragment with a zwitterionic cyanine dye to create a NIR probe (excitation/emission: 760/780 nm).
• Assessment of probe's aqueous solubility and stability.
• Evaluation of the probe's specific binding to TrkC-positive 4T1 breast cancer cells and tumor tissues.
• In vivo and ex vivo imaging studies in 4T1-tumor-bearing mice.

Main Results:

• A NIR fluorescent probe with good aqueous solubility was successfully synthesized.
• The probe demonstrated specific targeting to TrkC-positive metastatic breast cancer cells and tissues.
• In vivo and ex vivo fluorescence imaging successfully visualized tumors in mice injected with the probe.
• The probe facilitated the detection of metastatic breast tumors via its fluorescence signal.

Conclusions:

• The developed TrkC-targeting NIR probe is effective for in vivo imaging of metastatic breast tumors.
• This probe shows promise for diagnosing TrkC-positive metastatic breast cancer.
• Further investigation is warranted to advance this TrkC targeting agent for clinical diagnosis.