Chlorotoxin Conjugate for Tumor Margin Visualization

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Solution Overview

Problem

Current methods for intra-operative identification of tumor margins in cancer surgery are imprecise, particularly in the brain, where residual tumors may remain due to the inability to distinguish tumor tissue from normal brain tissue effectively, despite advances in imaging and monitoring.

Innovation Solution

A chlorotoxin conjugate with red or near-infrared emitting fluorescent moieties is developed, allowing for intra-operative visualization of cancerous tissues by binding specifically to cancer cells expressing matrix metalloproteinase-2 (MMP-2), enabling precise differentiation and removal of cancerous tissues during surgery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional surgical methods are used for tumor resection, then surgical judgment and standard imaging are employed, but the precision of tumor margin identification deteriorates leading to residual tumor recurrence

Engineering Contradiction:
Improvetumor margin identification precisionVSAvoidsurgical resection reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent employs fluorescent dyes that emit light in the red or near-infrared spectrum, causing tumor cells to visually stand out from normal tissue during surgery. This color/fluorescence change enables direct visual differentiation of tumor margins, directly improving measurement precision and reducing residual tumor recurrence

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The patent introduces fluorescently-labeled antibodies or other molecular probes as intermediaries that specifically bind to tumor-associated antigens or markers. These intermediaries act as mediators between the surgeon's visual system and the tumor cells, enabling precise identification of tumor margins that would otherwise be indistinguishable from normal tissue

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If surgical resection is extended to remove all visible tumor tissue, then tumor recurrence is reduced, but the risk of harming vital structures increases

Engineering Contradiction:
Improvetumor-free resection reliabilityVSAvoiddamage to vital structures
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

By causing tumor cells to fluoresce or change color, the patent provides clear visual boundaries between tumor and normal tissue. This enables surgeons to resect tumor margins with precision, removing all visible tumor tissue while stopping before damaging adjacent vital structures, thus improving resection reliability without increasing harm

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The fluorescently-labeled molecular probes serve as intermediaries that provide real-time visual feedback during surgery. This feedback mechanism allows surgeons to confidently extend resection to achieve complete tumor removal while the fluorescent marker continuously indicates the location of vital structures to avoid, balancing thoroughness with safety

Inventive Principle:
Principle #24Intermediary (Mediator)

3Loss of information

If conventional imaging guidance is used during surgery, then some tumor visualization is achieved, but the ability to distinguish tumor from normal brain tissue deteriorates

Engineering Contradiction:
Improvetumor tissue differentiation informationVSAvoidtumor boundary detection precision
Core Design Contradiction:
Loss of informationVSMeasurement precision

Solution Approach 1:

The patent applies fluorescent dyes that emit in the red or near-infrared spectrum, creating a visual contrast between tumor and normal tissue that is directly observable during surgery. This color/fluorescence information preserves and enhances tumor differentiation data, preventing information loss and improving boundary detection precision

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The fluorescently-labeled antibodies or molecular probes act as intermediaries that carry and display tumor-specific information in real-time during surgery. These intermediaries translate molecular-level tumor markers into visible fluorescent signals, preserving critical differentiation information and enabling precise boundary detection that conventional imaging cannot provide

Inventive Principle:
Principle #24Intermediary (Mediator)

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 chlorotoxin conjugate provides prolonged biophotonic imaging capabilities, allowing for the accurate visualization and removal of cancer cells, reducing the risk of residual tumors and improving surgical outcomes by enhancing the precision of tumor margin identification.

Implementation Method 1

one or more red or near infrared emitting fluorescent moieties covalently coupled to a chlorotoxin

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS8778310B2Fluorescent chlorotoxin conjugate and method for intra-operative visualization of cancer
Publication Date: 2014.07.15 FRED HUTCHINSON CANCER CENT
  • US8778310B2 patent drawing
  • US8778310B2 patent drawing
  • US8778310B2 patent drawing

AI summary

A chlorotoxin conjugate detectable by fluorescence imaging that allows for intra-operative visualization of cancerous tissues, compositions that include the chlorotoxin conjugate, and methods for using the chlorotoxin conjugate.