Cyclic Peptides for In Vivo Optical Imaging
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Solution Overview
Problem
Current methods for diagnosing colorectal cancer (CRC) lack effective early detection tools, particularly in vivo imaging agents that can selectively target and visualize cMet overexpression with minimal interference from endogenous tissues and rapid metabolism.
Innovation Solution
Development of cMet binding cyclic peptides labeled with optical reporter groups in the green to near-infrared region, specifically designed to minimize spectral overlap with biological tissues and protect against metabolism using metabolism inhibiting groups, allowing for selective and stable in vivo imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cMet binding peptides are used for in vivo imaging, then selective targeting of cMet is achieved, but rapid metabolism by endogenous enzymes and peptidases reduces imaging effectiveness
Solution Approach 1:
The patent combines cMet binding peptides with metabolism-inhibiting groups (such as N-terminal acetylation and C-terminal amide modification) to create composite molecular structures. These modifications protect the peptide termini from enzymatic degradation while preserving the central binding region's affinity for cMet, thereby extending in vivo circulation time and maintaining targeting reliability.
Solution Approach 2:
The patent modifies physical and chemical parameters of the peptide including cyclization to constrain the peptide backbone into a rigid structure, which protects against proteolytic degradation. Additionally, the use of non-natural amino acids and optimized hydrophobicity parameters further enhances metabolic stability while maintaining binding affinity.
2Measurement precision
If optical reporters are used for imaging, then in vivo visualization is achieved, but spectral overlap with endogenous tissues causes background interference
Solution Approach 1:
The patent selects optical reporters with emission wavelengths in the red to near-infrared region (650-900 nm), where endogenous tissue autofluorescence and absorption are minimized. This wavelength parameter optimization reduces background interference from hemoglobin, melanin, and other chromophores, thereby improving signal-to-noise ratio and imaging precision.
Solution Approach 2:
The patent replaces traditional mechanical or chemical detection methods with optical detection using fluorophores and quantum dots. This substitution enables non-invasive, real-time imaging with high sensitivity, as optical signals can be detected through tissue with minimal interference when appropriate wavelengths are selected.
3Measurement precision
If peptides are labelled with detectable groups, then imaging capability is achieved, but binding affinity for cMet may be reduced
Solution Approach 1:
The patent extracts the binding function and imaging function into separate modular components. The cMet binding peptide is designed as a distinct module with optimized amino acid sequence for high affinity, while the optical reporter is attached as a separate module through linkers. This modular design allows the binding region to maintain its native affinity while the imaging module provides detection capability.
Solution Approach 2:
The patent introduces flexible linkers and spacers as intermediary elements between the peptide binding region and the optical reporter group. These intermediaries prevent steric hindrance and conformational constraints that would otherwise interfere with peptide-cMet interactions, thereby preserving binding affinity while enabling imaging 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 cMet binding peptides provide effective in vivo optical imaging with high affinity for cMet, reducing background interference and maintaining selective targeting, thereby enhancing diagnostic imaging of CRC.
Implementation Method 1
an optical reporter imaging moiety suitable for imaging the mammalian body in vivo using light of green to near-infrared wavelength 500-1200 nm
Implementation Method 2
The green to near-infrared region (light of wavelength 500-1200 nm) is preferred, since that region has minimal spectral overlap with endogenous tissues and materials, such as haemoglobin, porphyrins, melanin, and collagen
Data Source
AI summary
The present invention relates to labelled cMet binding peptides suitable for optical imaging in vivo. The peptides are labelled with an optical reporter group suitable for imaging in the red to near-infrared region. Also disclosed are pharmaceutical compositions and kits, as well as in vivo imaging methods, especially of use in the detection, staging, diagnosis, monitoring of disease progression or monitoring of treatment of colorectal cancer (CRC).