EpCAM NIR Imaging Molecule for GI Tumor Margin Detection
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Solution Overview
Problem
Current methods for identifying and resecting gastrointestinal (GI) tumors, particularly after neoadjuvant therapy, face challenges in distinguishing between malignant tissue and chemoradiotherapy-induced necrosis or fibrosis, leading to high recurrence rates due to incomplete tumor removal.
Innovation Solution
A novel molecule, VB5-845D-800CW, comprising an anti-EpCAM antibody fragment conjugated to a NIR fluorescent dye, is administered to patients before surgery to enhance real-time visualization of EpCAM-positive tumors and lymph nodes, allowing for more accurate tumor localization and resection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If neoadjuvant chemoradiotherapy is administered to downstage tumors before surgery, then tumor size is reduced and recurrence rates decrease, but visual distinction between malignant cells and therapy-induced necrosis or fibrosis becomes difficult
Solution Approach 1:
The patent employs near-infrared fluorescent dyes that emit light at specific wavelengths to highlight malignant tissue. The fluorescent signal provides a distinct visual contrast between viable tumor cells and necrotic or fibrotic tissue, enabling surgeons to accurately identify tumor margins during resection after neoadjuvant therapy.
Solution Approach 2:
The patent uses fluorescently-labeled antibodies or molecular probes as intermediaries that specifically bind to tumor-associated antigens or biomarkers. These probes act as mediators between the surgeon's visual system and the invisible molecular differences between malignant and benign tissue, translating biochemical information into visible fluorescent signals.
2Loss of information
If pre-operative imaging modalities are used to predict tumor localization, then surgical planning is improved, but accurate margin discrimination during surgery becomes challenging after neoadjuvant therapy
Solution Approach 1:
The patent administers the fluorescent imaging agent pre-operatively, allowing sufficient time for the probe to accumulate in tumor tissue before surgery. This preliminary action ensures that the tumor and its margins are already highlighted with fluorescent signal when the patient enters the operating room, providing continuous visual guidance throughout the resection process.
Solution Approach 2:
The patent replaces traditional mechanical or visual assessment methods (palpation, gross inspection) with optical detection using near-infrared fluorescence imaging. This substitution allows for real-time, objective visualization of tumor margins that is not limited by human sensory constraints or affected by tissue changes from neoadjuvant therapy.
3Reliability
If invasive resections are performed to remove infiltrative malignant tissue, then complete tumor removal is achieved, but surgical complexity and patient morbidity increase
Solution Approach 1:
The fluorescent imaging agent causes malignant tissue to emit visible near-infrared fluorescence, creating a clear visual distinction between tumor and normal tissue. This optical contrast allows surgeons to precisely define resection margins without needing to perform extensive invasive dissection, thereby achieving complete tumor removal with less surgical complexity.
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
VB5-845D-800CW provides clear intraoperative visualization of GI tumors and lymph nodes, improving surgical accuracy and reducing recurrence rates by enhancing tumor-to-background ratios, even after neoadjuvant therapy.
Implementation Method 1
an antibody or antibody fragment capable of specifically targeting EpCAM
Implementation Method 2
A preferred NIR fluorescent dye is IRDye 800CW, a near infrared fluorescent dye (800 nm)
Data Source
AI summary
Herein is provided a novel molecule and infusion solutions containing the molecule useful for the detection and imaging of EpCAM positive tumors as well as lymph nodes, such as, but not limited to, lower GI (i.e. colorectal) and upper GI (i.e. gastric and esophageal) cancers. The molecule is comprised of an antibody or antibody fragment capable of specifically targeting EpCAM conjugated to a NIR fluorescent dye. A preferred antibody fragment is VB5-845D and a preferred NIR fluorescent dye is IRDye 800CW. Aspects of the invention provide a method of intraoperative tumor visualization of EpCAM expressing primary tumors and lymph nodes.