FAP-Targeted NIR Conjugates for CAF Visualization During Surgery

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Solution Overview

Problem

Current methods fail to efficiently image and surgically remove cancer-associated fibroblasts (CAFs) in the tumor microenvironment, as existing NIR dye conjugates target only cancer cells and not stromal cells.

Innovation Solution

Development of conjugates comprising a fibroblast activation protein (FAP) inhibitor linked to a bivalent linker and a near-infrared (NIR) dye or therapeutic agent, allowing for targeted imaging and treatment of CAFs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing NIR dye conjugates are used to target cancer cells, then cancer cells can be imaged, but stromal cells (CAFs) cannot be imaged

Engineering Contradiction:

Improveimaging capabilityVSAvoidtargeting scope

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent applies universality by designing a conjugate system that can target multiple cell types (cancer cells and stromal cells/CAFs) simultaneously through the FAP inhibitor component. The FAP inhibitor provides broad targeting capability across different tumor microenvironment cells, making the imaging agent versatile for comprehensive tumor visualization rather than limited to single cell type targeting

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Measurement precision

If conventional imaging agents are used, then only cancer cells are visible during surgery, but stromal cells remain undetected

Engineering Contradiction:

Improvedetection accuracyVSAvoidstromal cell information

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The patent uses the FAP inhibitor as an intermediary molecule that specifically binds to fibroblast activation protein on stromal cells, enabling their detection. This intermediary targeting mechanism allows the imaging conjugate to reveal stromal cell locations that would otherwise be invisible during surgical procedures, preventing loss of critical anatomical information

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If tumor resection is performed without stromal cell visualization, then cancer cells can be removed, but residual stromal cells may remain

Engineering Contradiction:

Improvesurgical efficiencyVSAvoidcomplete tumor removal

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent employs fluorescence emission (color change) of the NIR dye upon excitation to visually distinguish stromal cells from surrounding tissue during surgery. This optical signal transformation enables surgeons to see the complete tumor architecture including stromal components, ensuring reliable and complete tumor resection while maintaining surgical efficiency

Inventive Principle:

Principle #32Color changes

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

Enables effective visualization and surgical removal of CAFs, enhancing tumor resection by highlighting stromal cells through fluorescence-guided surgery.

Implementation Method 1

X comprises a near infrared (NIR) dye

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS12397069B2Fibroblast activation protein (FAP)-targeted imaging and therapy

Publication Date: 2025.08.26 PURDUE RES FOUND

AI summary

The present teachings relate generally to conjugates and methods for imaging a tumor microenvironment in a patient, and to conjugates and methods for imaging cancer-associated fibroblasts (CAFs) in the tumor microenvironment of a patient. The present teachings relate generally to method of making conjugates comprising a fibroblast activation protein (FAP) inhibitor.