Far-Red Spray-On Imaging Probes for FAP-Targeted Cancer Surgery

Area of Science:

• Oncology
• Medical Imaging
• Bioconjugate Chemistry

Background:

• Fluorescence-guided surgery (FGS) enhances tumor margin detection but often relies on systemic probes that clear slowly.
• Topical spray-on probes (SOP) offer advantages in dose, on-demand application, and improved contrast for FGS.

Purpose of the Study:

• To discover and characterize a novel far-red fluorescent imaging agent for topical administration as a spray-on probe (SOP).
• To evaluate the efficacy of the SOP for intraoperative tumor margin delineation targeting fibroblast activation protein alpha.

Main Methods:

• Synthesis and screening of multiple far-red fluorescent probes for SOP application.
• Evaluation of probe characteristics including tumor-to-background ratio and imaging contrast.
• Assessment of the optimal SOP's performance in rapid tumor margin delineation at low doses.

Main Results:

• Only 1 of 10 synthesized probes exhibited optimal imaging and biological properties.
• The lead SOP (FTF-Cy5) significantly increased tumor-to-background ratio by 5-15 fold.
• FTF-Cy5 rapidly delineated tumor margins (<10 min) at a low dose (5 μM) after topical application and washing.

Conclusions:

• The developed far-red SOP (FTF-Cy5) shows significant potential as an intraoperative tumor margin delineation tool.
• This spray-on approach simplifies surgical workflows and may lead to more complete cancer resections.
• Far-red fluorescence imaging systems can be utilized with SOPs for enhanced surgical guidance.