Collagen Turnover Imaging Agents via Segmentation

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Solution Overview

Problem

Current imaging modalities struggle to detect collagen turnover associated with fibrosis, as they primarily target mature collagen rather than ongoing matrix remodeling, which is crucial for tracking active fibrogenesis and resolution of fibrosis.

Innovation Solution

Development of imaging agents that bind to single-stranded collagen, such as 99mTc-His6-(GPO)9, which utilize a poly-histidine tag and GPO repeats linked by a flexible linker to specifically target and image collagen turnover using SPECT/CT imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If structural imaging modalities (MRI, CT) are used to image collagen, then tissue structure can be visualized, but information on active collagen turnover and disease activity is lost

Engineering Contradiction:

Improvedetection of collagen turnoverVSAvoidinformation on disease activity

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The patent segments the collagen imaging problem by creating distinct imaging agents that target different collagen states: one agent targets triple-helical mature collagen while another targets single-stranded turnover collagen. This segmentation allows simultaneous visualization of both structural collagen and active turnover processes, resolving the contradiction between visualizing structure and detecting activity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces molecular imaging agents as intermediaries that bridge the gap between structural imaging and functional detection. These agents bind specifically to collagen in different conformational states and carry detectable labels, enabling the detection of collagen turnover activity without compromising structural visualization capability

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If imaging agents target mature collagen, then collagen structure is visualized, but active fibrogenesis and resolution processes cannot be detected

Engineering Contradiction:

Improvedetection of active remodelingVSAvoidmonitoring of fibrosis progression

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent applies local quality by designing imaging agents with specific molecular structures that confer selective affinity for different collagen conformations. One agent has structural features optimized for binding triple-helical collagen, while another has features optimized for binding single-stranded collagen. This local structural differentiation enables reliable detection of active remodeling processes while maintaining measurement precision for fibrosis progression

Inventive Principle:

Principle #3Local quality

3Loss of time

If there is a lag before therapeutic effects are reflected on tissue structure, then structural imaging can detect changes, but early treatment response cannot be monitored

Engineering Contradiction:

Improvedetection time of treatment effectVSAvoidtracking of therapeutic intervention

Core Design Contradiction:

Loss of timeVSReliability

Solution Approach 1:

The patent enables preliminary detection of treatment effects by targeting single-stranded collagen, which appears early in the collagen turnover process before mature fibrotic structures form. This allows clinicians to detect treatment response at the molecular level before structural changes become visible on conventional imaging, reducing the time loss in detecting therapeutic effects

Inventive Principle:

Principle #10Preliminary action

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 the detection of collagen turnover in fibrotic diseases by highlighting active remodeling processes, allowing for better monitoring of fibrosis progression and treatment efficacy.

Implementation Method 1

imaging agents that bind to single-stranded collagen, such as 99mTc-His6-(GPO)9, which utilize a poly-histidine tag and GPO repeats linked by a flexible linker to specifically target and image collagen turnover

Methodology Applied

Scientific EffectSpecific binding:

Implementation Method 2

detecting a signal from the compound of formula (I) within the subject. In certain embodiments, the signal is detected using single photon emission computed tomography (SPECT) imaging

Methodology Applied

Scientific EffectSPECT imaging detection:

Data Source

PatentUS20240298987A1Compounds For Molecular Imaging of Collagen Turnover and Methods Using Same

Publication Date: 2024.09.12 YALE UNIVERSITY

AI summary

In one aspect, the present disclosure relates to an imaging agent comprising a detectable moiety covalently bound or coordinated to a “Moiety A” selected from a peptide, a chelator, or an organic compound comprising a leaving atom or a leaving group that can be substituted with a radioisotope. “Moiety A” is covalently bound to a flexible linker which is further covalently bound to a polypeptide of between 2 and 20 glycine-proline-hydroxyproline repeats. In certain embodiments, the detectable moiety comprises a radioisotope or metal. In another aspect, the disclosure relates to a method of using the imaging agents of the present disclosure to detect collagen turnover in a subject.