Fluorescent Conjugate for Tumor Resection Guidance
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Solution Overview
Problem
Current cancer photodetection methods, such as those using hematoporphyrin derivatives, suffer from low selectivity for cancerous tissues and high photosensitization, limiting their clinical utility in visualizing tumors during surgery.
Innovation Solution
Development of a fluorescent conjugate comprising a cyanine derivative fluorochrome coupled to a targeting moiety, such as a chimeric monoclonal antibody, which specifically binds to tumor markers like carcinoembryonic antigen (CEA), allowing for improved visualization of tumors under near-infrared light.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If hematoporphyrin derivatives are used for photodetection, then tumor visualization is achieved, but selectivity for cancerous tissues is low and photosensitization is high
Solution Approach 1:
The patent combines a fluorochrome (for optical visualization) with a tumor-specific targeting moiety (such as monoclonal antibodies or peptides) to create a composite conjugate. This composite structure provides both high tumor specificity through the targeting component and strong fluorescent signal through the fluorochrome, while avoiding the photosensitization issues of hematoporphyrin derivatives.
Solution Approach 2:
The fluorescent conjugate is designed to concentrate fluorescence signal specifically at tumor locations through the targeting moiety's selective binding to tumor markers. This local concentration of fluorescent activity enhances detection precision while minimizing background signal and harmful photosensitization effects in non-target tissues.
2Measurement precision
If conventional fluorochromes are used, then tumor visualization is possible, but tissue penetration is low due to short excitation and emission wavelengths
Solution Approach 1:
The patent selects fluorochromes with optimized spectral parameters, specifically those with longer excitation and emission wavelengths in the red to near-infrared region (650-900 nm). This parameter change in the fluorochrome's optical properties enables deeper tissue penetration while maintaining sufficient fluorescence signal for tumor visualization.
3Measurement precision
If autofluorescence from non-cancerous tissues is reduced, then detection sensitivity improves, but this requires avoiding laser light that induces autofluorescence
Solution Approach 1:
The patent employs fluorochromes with excitation and emission wavelengths in the red-near infrared range (650-900 nm), where biological tissues exhibit minimal autofluorescence. By changing the operational wavelength parameters away from the blue-green range that causes strong autofluorescence, the system achieves high detection sensitivity without significant laser-induced background interference.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The conjugate provides high tumor specificity, sensitivity, and stability, enabling the detection of small tumor lesions and guiding surgeons during resection surgery, thereby improving cancer resection outcomes.
Implementation Method 1
a fluorochrome moiety F coupled to a targeting moiety T, wherein moiety F has the formula (I)... allowing for improved visualization of tumors under near-infrared light
Data Source
AI summary
The invention provides a conjugate with fluorochrome moiety F coupled to a targeting moiety T. Moiety F is described by formula (I), and the targeting moiety T is characterized in that it has affinity to a tumor marker, such as an antibody or antibody fragment. The conjugate may be used for tumor diagnostics including photodetection of tumor nodules during resection surgery.