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AND-gate contrast agents for enhanced fluorescence-guided surgery
John C Widen1, Martina Tholen1, Joshua J Yim1,2
1Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Abstract:
Surgical resection of tumours requires precisely locating and defining the margins between lesions and normal tissue. However, this is made difficult by irregular margin borders. Although molecularly targeted optical contrast agents can be used to define tumour margins during surgery in real time, the selectivity of the contrast agents is often limited by the target being expressed in both healthy and tumour tissues. Here, we show that AND-gate optical imaging probes that require the processing of two substrates by multiple tumour-specific enzymes produce a fluorescent signal with significantly improved specificity and sensitivity to tumour tissue. We evaluated the performance of the probes in mouse models of mammary tumours and of metastatic lung cancer, as well as during fluorescence-guided robotic surgery. Imaging probes that rely on multivariate activation to selectively target complex patterns of enzymatic activity should be useful in disease detection, treatment and monitoring.
Insights
New AND-gate optical imaging probes improve tumor margin detection. These probes require multiple tumor-specific enzymes for activation, enhancing specificity and sensitivity in real-time surgical guidance.
Area of Science:
- Biomedical Engineering
- Optical Imaging
- Surgical Oncology
Background:
- Precise surgical resection of tumors is challenging due to irregular tumor margins.
- Current optical contrast agents for real-time tumor margin delineation have limited specificity, as targets are often present in healthy tissues.
Purpose of the Study:
- To develop and evaluate novel AND-gate optical imaging probes for enhanced specificity and sensitivity in identifying tumor margins during surgery.
Main Methods:
- Designed AND-gate optical imaging probes activated by two substrates processed by multiple tumor-specific enzymes.
- Evaluated probe performance in mouse models of mammary tumors and metastatic lung cancer.
- Assessed probe utility in fluorescence-guided robotic surgery.
Main Results:
- AND-gate probes demonstrated significantly improved specificity and sensitivity to tumor tissue compared to conventional agents.
- Multivariate activation strategy enabled selective fluorescent signal generation based on complex enzymatic patterns.
- Successful application in preclinical tumor models and robotic surgery settings.
Conclusions:
- AND-gate optical imaging probes offer a promising approach for accurate tumor margin definition.
- Multivariate activation strategies enhance disease detection, treatment, and monitoring capabilities.
- These advanced probes have potential applications in various oncological interventions.
