An agent for optical imaging of TrkC-expressing, breast cancer

Area of Science:

• Biochemistry
• Molecular Biology
• Medical Imaging

Background:

• Tropomyosin receptor kinase C (TrkC) is highly expressed in metastatic cancers like breast cancer, melanoma, glioblastoma, and neuroblastoma.
• Previous TrkC-targeting probes for photodynamic therapy showed tumor ablation but modifications for near-infrared imaging presented challenges.
• Modifications for imaging risked increased molecular mass or compromised TrkC binding affinity.

Purpose of the Study:

• To investigate if modifying TrkC-targeting probes for near-infrared optical imaging could be achieved without compromising TrkC binding.
• To synthesize and evaluate a novel aza-BODIPY probe (1a) designed to replace a spacer fragment in existing probes.
• To assess the probe's binding specificity and contrast in TrkC-positive versus healthy tissues.

Main Methods:

• Synthesis of a novel aza-BODIPY probe (1a) replacing a spacer in a known TrkC ligand.
• Evaluation of probe 1a binding in live TrkC+ breast cancer cell cultures.
• Histochemical studies and in vivo assessment in a murine model using probe 1a and a non-binding isomer (1b) as a negative control.

Main Results:

• The synthesized aza-BODIPY probe (1a) successfully binds TrkC-expressing breast cancer cells in vitro.
• Probe 1a demonstrated specific binding to TrkC+ tissues in histochemical studies and in vivo.
• The probe exhibited good contrast against healthy tissues and significantly stronger binding than the negative control probe (1b).

Conclusions:

• The novel aza-BODIPY probe (1a) is a viable candidate for TrkC-targeted near-infrared optical imaging.
• This probe design strategy successfully maintained TrkC binding affinity while enabling potential imaging applications.
• The findings support the development of targeted imaging agents for TrkC-expressing cancers.