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Updated: Jun 20, 2026
Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
Published on: July 17, 2012
Far-Red Spray-On Imaging Probes for FAP-Targeted Cancer Surgery
Zachary Rabinowitz1, Riley J Deutsch-Williams1, Ralph Weissleder1,2
1Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, Massachusetts 02114, United States.
Abstract:
Fluorescence-guided surgery (FGS) using fluorescent imaging probes is an emerging technology that enables tumor margin detection at potentially higher accuracy than is possible with traditional means. Most FGS imaging probes are administered systemically, many hours before a planned surgery, and must have cleared the bloodstream once surgery is initiated, so as not to contaminate the operative field. Topical administration of specially designed conjugates in the form of spray-on probes (SOP) offers the advantage of much lower doses, on-demand use, and result in far higher achievable image contrast. Here we report the discovery and characterization of a far-red SOP imaging agent targeting fibroblast activation protein alpha. We show that only 1 out of 10 synthesized probes has appropriate imaging and biological characteristics, increasing tumor-to-background ratio by 5-15 fold. The optimal SOP (FTF-Cy5) was able to delineate tumor margins rapidly (<10 min) when sprayed on at a low dose (5 μM) followed by a short washing step. These results suggest that the lead far-red SOP has the potential to be utilized as a spray-on intraoperative tumor margin delineation tool using far-red fluorescence imaging systems in the operating room, thereby simplifying surgical workflows and enabling more complete cancer resections in the future.
Insights
Spray-on probes (SOP) offer a novel approach to fluorescence-guided surgery (FGS) for enhanced tumor margin detection. This study identified an optimal far-red SOP that rapidly delineates tumor margins with high contrast.
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.
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