Cleavable Peptide Radionuclide Composition for SPECT Enzyme Imaging

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Solution Overview

Problem

Current activatable optical contrast agents for imaging enzyme activity suffer from poor tissue penetration, limiting their clinical translatability, necessitating a nuclear alternative that can detect enzyme activity and image diseases associated with it.

Innovation Solution

Development of a composition comprising a cleavable peptide with two spectrally distinct radionuclides separated by an enzyme-susceptible site, allowing for simultaneous detection and imaging of enzyme activity using Single Photon Emission Computed Tomography (SPECT).

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If optical contrast agents are used to detect enzyme activity, then molecular and biological specificity is improved, but tissue penetration is poor

Engineering Contradiction:
Improveenzyme activity detection specificityVSAvoidtissue penetration limitation
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces optical imaging mechanisms with nuclear imaging mechanisms by using radionuclides that emit gamma rays detectable by SPECT. This substitution overcomes the tissue penetration limitation of optical agents while maintaining the ability to detect enzyme activity through the cleavable peptide-radionuclide construct.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the detection parameter from optical signal to nuclear radiation signal. By using radionuclides with distinct gamma ray energies that can be spectrally differentiated, the system achieves both deep tissue penetration and specific enzyme activity detection through the cleavable peptide mechanism.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If two radionuclides are used for simultaneous detection, then imaging capability is improved, but spectral differentiation complexity increases

Engineering Contradiction:
Improvesimultaneous detection capabilityVSAvoidspectral differentiation requirement
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent assigns different spectral properties (distinct gamma ray energies) to each radionuclide in the system. This local differentiation of spectral characteristics allows simultaneous detection of multiple targets while enabling clear distinction between signals through energy discrimination in SPECT imaging.

Inventive Principle:
Principle #3Local quality

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 non-invasive monitoring of enzyme activity and therapeutic response, potentially identifying nonresponders early and providing a more effective treatment approach by overcoming the tissue penetration limitations of optical agents.

Implementation Method 1

two distinct radionuclides, wherein the radionuclides are separated by a site susceptible to cleavage and can be spectrally differentiated

Methodology Applied
Scientific EffectGamma ray emission: Radioactive Decay

Implementation Method 2

imaging the subject for a signal corresponding to the first and second radionuclide

Methodology Applied
Scientific EffectSingle Photon Emission Computed Tomography (SPECT): Tomography

Implementation Method 3

a cleavable peptide and two distinct radionuclides, wherein the radionuclides are separated by a site susceptible to cleavage by an enzyme

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentUS12257327B2Compositions and methods for treatment and imaging using nanoparticles
Publication Date: 2025.03.25 WASHINGTON UNIV IN SAINT LOUIS
  • US12257327B2 patent drawing
  • US12257327B2 patent drawing
  • US12257327B2 patent drawing

AI summary

The present invention encompasses compositions comprising two spectrally distinct radionuclides separated by a site susceptible to cleavage. Compositions of the invention may be used to detect enzyme activity and/or image diseases associated with said enzyme activity.