Real-Time Detection of Colorectal Cancer Using Topical Application of a pH-Activatable Fluorophore

Area of Science:

• Medical imaging
• Surgical oncology
• Fluorescent probes

Background:

• Standard treatment for locally advanced rectal cancer involves neoadjuvant chemoradiation therapy (nCRT) followed by surgery, but this can lead to significant morbidity and incomplete resections due to poor tumor visualization.
• Current imaging techniques inadequately identify complete responders to nCRT, impacting the success of the watch-and-wait strategy and leading to tumor regrowth in approximately 30% of cases.

Purpose of the Study:

• To develop a novel imaging agent, PH10, for improved assessment of nCRT response and enhanced intraoperative tumor visualization.
• To create a rapid, tumor-specific, pH-activatable near-infrared (NIR) fluorescent probe for clinical application.

Main Methods:

• PH10, a small-molecule cyanine analog, was evaluated in murine models and on human rectal tumor specimens (n=11).
• Assessed fluorescence activation, tumor specificity, and tumor-to-background ratio (TBR) in vivo and ex vivo within clinically relevant timeframes.

Main Results:

• PH10 demonstrated rapid and specific tumor visualization, achieving a median TBR of 3.2 within 1 minute in vivo and 2.2 within 10 minutes ex vivo.
• The probe showed high specificity for tumor tissue in acidic microenvironments without systemic administration or prolonged incubation.

Conclusions:

• PH10 is a promising topical NIR agent for real-time tumor detection in colorectal cancer endoscopy and surgery.
• Its rapid kinetics and pH-activatable mechanism suggest potential for clinical translation and broader application in solid cancers with acidic microenvironments.