FAP-Targeted MRI Conjugate for Contrast and Toxicity Trade-off

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Solution Overview

Problem

Current MRI agents lack specificity due to non-targeted uptake, resulting in reduced contrast and increased toxicity during imaging of cancers and soft tissues.

Innovation Solution

Development of a conjugate comprising a small molecule ligand (FL) that specifically binds to fibroblast activation protein (FAP) linked with a magnetic resonance imaging (MRI) agent (IA) via a linker (L), allowing targeted imaging by specifically binding to FAP-expressing cells or tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If non-targeted MRI agents are used, then imaging coverage is broad, but contrast is reduced and toxicity is increased

Engineering Contradiction:
Improveimaging contrastVSAvoidtoxicity
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The MRI agent system is segmented into two functional components: a targeting moiety (FL radical) that specifically binds to FAP-expressing cells, and an MRI agent radical (IA) that provides the imaging function. This segmentation allows the targeting component to direct the agent specifically to diseased tissue while the MRI component provides contrast, thereby improving both contrast and reducing toxicity through selective accumulation at the target site.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The linker L serves as an intermediary component that chemically connects the targeting moiety (FL radical) to the MRI agent radical (IA). This intermediary structure enables the stable integration of the targeting function and imaging function into a single conjugate molecule, allowing the targeted MRI agent to maintain both its specific binding capability and its imaging contrast function simultaneously.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If non-targeted MRI agents are used, then distribution is uniform, but specificity is lost

Engineering Contradiction:
Improveimaging specificityVSAvoidconjugate structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The MRI agent is constructed as a composite conjugate molecule comprising three distinct functional radicals: the FL radical (targeting moiety with specific FAP binding capability), the linker L (connecting structure), and the IA radical (MRI contrast agent). This composite structure integrates targeting specificity and imaging functionality into a single molecular entity, achieving high imaging specificity while the modular design helps manage structural complexity.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The conjugate structure is designed to perform multiple functions simultaneously: the FL radical provides specific targeting to FAP-expressing cells, the linker L provides stable chemical connection, and the IA radical provides MRI contrast. This multi-functionality within a single conjugate molecule achieves both high specificity and broad applicability for imaging various FAP-positive conditions.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 enables enhanced contrast and reduced toxicity by specifically targeting FAP-expressing cells or tissues, improving the accuracy and safety of MRI imaging for cancer and other conditions.

Implementation Method 1

FL is a radical of a small molecule ligand that specifically binds with fibroblast activation protein (FAP)

Methodology Applied
Scientific EffectMolecular binding:

Implementation Method 2

The paramagnetic contrast agent can comprise gadolinium (Gd3+), manganese (Mn2+), or dysprosium (Dy3+)

Methodology Applied
Scientific EffectParamagnetism:

Data Source

PatentUS20230405153A1Fibroblast activation protein-targeted magnetic resonance imaging agents, compositions, and methods of use
Publication Date: 2023.12.21 PURDUE RES FOUND
  • US20230405153A1 patent drawing
  • US20230405153A1 patent drawing
  • US20230405153A1 patent drawing

AI summary

A conjugate comprising FL-L-IA, wherein FL is a radical of a small molecule ligand that specifically binds with fibroblast activation protein (FAP), L is a linker, which binds an FL to IA, and IA is a radical of a magnetic resonance imaging (MRI) agent, or a pharmaceutically acceptable salt thereof; a composition comprising same; and a method of using the conjugate or composition to image cells, a tissue, or an organ that express(es) FAP with magnetic resonance imaging.