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Published on: September 19, 2014
Near-Infrared Fluorogenic Spray for Rapid Tumor Sensing
Ching-Hsuan Tung1, Myung Shin Han1, Zhenhua Shen1
1Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York 10021, United States.
Abstract:
Surgical resection of cancerous tissues is a critical procedure for solid tumor treatment. During the operation, the surgeon mostly identifies the cancerous tissues by naked-eye visualization under white light without aid, therefore, the outcome heavily relies on the surgeon's experience. A near-infrared pH-responsive fluorogenic dye, CypH-11, was designed to be used as a sensitive cancer spray to highlight cancerous tissues during surgical operations, minimizing the surgeon's subjective judgment. CypH-11, pKa 6.0, emits almost no fluorescence at neutral pH but fluoresces brightly in an acidic environment, a ubiquitous consequence of cancer cell proliferation. After topical application, CypH-11 was absorbed quickly, and its fluorescence signal in the cancerous tissue was developed within a minute. The signal-to-background ratio was 1.3 and 1.5 at 1 and 10 min, respectively. The fluorogenic property and near-instant signal development capability enable the "spray-and-see" concept. This fast-acting CypH-11 spray could be a handy and effective tool for fluorescence-guided surgery, identifying small cancerous lesions in real time for optimal resection without systemic toxicity.
Insights
A new near-infrared dye, CypH-11, acts as a cancer spray, highlighting tumors during surgery. This pH-responsive agent provides real-time visualization, improving cancer resection accuracy and reducing surgeon reliance on visual cues.
Area of Science:
- Oncology
- Surgical Innovation
- Biomedical Engineering
Background:
- Surgical resection of solid tumors relies heavily on surgeon's visual identification of cancerous tissues.
- Current methods lack objective tools, making outcomes dependent on surgeon experience.
- Need for improved real-time visualization during surgery to enhance precision.
Purpose of the Study:
- To develop and evaluate CypH-11, a novel near-infrared pH-responsive fluorogenic dye.
- To assess CypH-11's efficacy as a cancer spray for highlighting cancerous tissues during surgery.
- To enable a "spray-and-see" approach for fluorescence-guided surgery.
Main Methods:
- Design of CypH-11, a pH-responsive fluorogenic dye with a pKa of 6.0.
- Topical application of CypH-11 spray to cancerous tissues.
- Evaluation of fluorescence signal development and signal-to-background ratio over time.
- Assessment of real-time visualization capabilities for identifying cancerous lesions.
Main Results:
- CypH-11 exhibits minimal fluorescence at neutral pH and bright fluorescence in acidic tumor microenvironments.
- Rapid absorption and fluorescence signal development within one minute post-application.
- Achieved signal-to-background ratios of 1.3 at 1 minute and 1.5 at 10 minutes.
- Demonstrated potential for real-time identification of small cancerous lesions.
Conclusions:
- CypH-11 spray offers a fast-acting, effective tool for fluorescence-guided surgery.
- The dye minimizes subjective judgment by providing clear visualization of cancerous tissues.
- This approach could lead to optimal tumor resection with reduced systemic toxicity.

