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Erasable FAP Targeted Spray-On Probe for Fluorescence-Guided Surgery
Zachary Rabinowitz1, Riley J Deutsch-Williams1, Ralph Weissleder1,2
1Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Abstract:
Fluorescence-guided surgery is an emerging clinical field that aims to improve cancer detection in real-time, enabling spot-on therapeutic decisions. The use of fluorescent affinity probes has primarily involved systemically injected probes and, more recently, "spray-on probes". A current challenge has been to develop "turn-off" probes that can be inactivated by a UV light pulse and reduce background noise during iterative decision-making. Here, we report on the first development of a FAP-targeted erasable spray-on probe (ESOP). The probe consists of three components: (i) a highly bright, yellow light-emitting rhodamine dye, (ii) a photo-responsive linear triazene linker, and (iii) a FAP affinity ligand. We demonstrate that this probe could enable highly sensitive tumor-specific margin visualization within minutes after a spray-on application. Moreover, we show that the fluorescent signals could be fully erased with a 2-min UV-light pulse in tissue, permitting iterative staining applications with consistently high tumor-to-background ratios (TBRs). ESOP targeted against cancer or host tissue is feasible and is likely to yield transformative impacts on next-generation cancer surgeries, ultimately improving patient care.
Insights
Researchers developed a novel erasable spray-on probe (ESOP) for fluorescence-guided surgery. This innovative probe enhances real-time cancer detection and allows for iterative visualization by erasing signals with UV light.
Area of Science:
- Biomedical Engineering
- Surgical Oncology
- Molecular Imaging
Background:
- Fluorescence-guided surgery (FGS) enhances real-time cancer detection and therapeutic decisions.
- Current fluorescent affinity probes (FAPs) include systemically injected and spray-on types.
- A key challenge in FGS is developing 'turn-off' probes to reduce background noise during iterative procedures.
Purpose of the Study:
- To develop and characterize the first FAP-targeted erasable spray-on probe (ESOP).
- To evaluate the probe's efficacy in sensitive tumor-specific margin visualization.
- To demonstrate the probe's capacity for iterative applications via UV-induced signal erasure.
Main Methods:
- Development of a novel ESOP comprising a rhodamine dye, a photo-responsive triazene linker, and a FAP affinity ligand.
- Application of the ESOP as a spray onto tissue for real-time imaging.
- Erasure of fluorescent signals using a 2-minute UV light pulse for iterative staining.
Main Results:
- The ESOP enabled highly sensitive, tumor-specific margin visualization within minutes of spray application.
- Fluorescent signals were completely erased by UV light, allowing for repeated staining.
- Consistently high tumor-to-background ratios (TBRs) were achieved in iterative applications.
Conclusions:
- FAP-targeted ESOPs are feasible for both cancer and host tissue targeting.
- This technology has the potential to transform next-generation cancer surgeries.
- The development of ESOPs promises to significantly improve patient care through enhanced surgical precision.
