Truncated Evans Blue–Modified RGD Dimer Peptide for Tumor Retention
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Solution Overview
Problem
Existing radionuclide labeled RGD cyclic peptides have low tumor uptake and short retention time, requiring high doses and frequent administration, which increases adverse side effects and limits clinical application.
Innovation Solution
Development of a truncated Evans Blue modified RGD dimer peptide that binds to serum albumin, acting as a delivery vector to prolong the peptide's half-life and enhance tumor uptake and retention time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If radionuclide labeled RGD cyclic peptides are used for tumor imaging and therapy, then tumor-specific binding is achieved, but blood half-life is short and metabolic clearance is rapid
Solution Approach 1:
The patent creates a composite structure by conjugating RGD cyclic peptide with truncated Evans Blue (tEB) through covalent bonding. The tEB component binds to serum albumin with high affinity, forming a circulating complex that extends the half-life of the RGD peptide while maintaining its tumor-targeting capability through the intact RGD sequence
Solution Approach 2:
The truncated Evans Blue acts as an intermediary carrier that bridges the RGD peptide and serum albumin. It provides a stable connection point on the peptide while offering high-affinity binding sites for albumin, thereby mediating the interaction between the tumor-targeting peptide and the long-circulating albumin protein
2Duration of action of moving object
If polyethylene glycol modification is applied to reduce clearance rate, then blood half-life is extended, but immunogenicity increases and bioavailability decreases
Solution Approach 1:
The patent changes the chemical structure parameter by using truncated Evans Blue instead of polyethylene glycol as the modifying group. This structural substitution maintains the ability to extend circulation time through albumin binding while avoiding the immunogenicity problems associated with PEG modification
3Quantity of substance
If high dose and frequent administration are implemented to achieve therapy purpose, then tumor uptake is sufficient, but adverse side effects increase
Solution Approach 1:
The patent creates a dynamic circulation system where the RGD-tEB-albumin complex continuously circulates in the bloodstream, dynamically accumulating at tumor sites through repeated binding events. The extended half-life allows the compound to maintain therapeutic levels at the tumor over time, reducing the need for high doses and frequent administration
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 RGD dimer peptide improves tumor uptake and retention time, facilitating effective diagnosis and treatment of diseases with integrin αvβ3 over-expression.
Implementation Method 1
it can effectively bind to serum albumin through a truncated Evans Blue structure to use the albumin as a delivery vector of the RGD dimer peptide
Implementation Method 2
A polypeptide containing an arginine-glycine-aspartic acid (RGD) sequence can specifically bind to the integrin αvβ3
Data Source
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AI summary
The present invention provides an RGD dimer compound, a preparation method therefor and use thereof, and relates to the fields of nuclear medicine and molecular imaging. The RGD dimer compound has a structure shown in Formula (I) or Formula (I-1). The present invention further provides a radionuclide labeled compound with the RGD dimer compound shown in Formula (I-1) as a ligand, a pharmaceutical composition containing or composed of the RGD dimer compound, and a kit containing or composed of the RGD dimer compound or the pharmaceutical composition. The present invention further provides use of the RGD dimer compound or the pharmaceutical composition in diagnosis or treatment of diseases characterized by over-expression of an integrin αvβ3. The RGD dimer compound and the radionuclide labeled compound of the present invention have higher tumor uptake and a longer retention time and are expected to be used in diagnosis or treatment of diseases characterized by over-expression of the integrin αvβ3.