PSMA-Targeted NIR Dye Linker Optimization for Tumor Imaging
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Solution Overview
Problem
Current PSMA-targeted NIR dyes for prostate cancer diagnosis and surgery face challenges such as low tumor specificity, slow skin clearance, and poor pharmacokinetic properties, leading to suboptimal tumor-to-background ratios and prolonged hospital stays.
Innovation Solution
Development of PSMA-targeted ligands conjugated to NIR dyes via specific linkers, optimizing spacer lengths and amino acid sequences to enhance stability, solubility, and affinity, allowing for faster tumor accumulation and clearance, thereby improving imaging and surgical guidance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If PSMA-targeted NIR dyes are used for prostate cancer diagnosis and surgery, then tumor detection capability is improved, but tumor specificity is low leading to poor tumor-to-background ratios
Solution Approach 1:
The patent modifies the chemical structure of NIR dyes by changing parameters such as spacer length, amino acid sequence, and linker type to optimize binding affinity and specificity for PSMA. These parameter changes improve tumor-to-background ratios while maintaining detection capability
Solution Approach 2:
The patent creates composite structures by conjugating PSMA-targeted ligands with NIR dye molecules through specific linkers. This composite approach combines the targeting specificity of ligands with the imaging capability of NIR dyes, enhancing both tumor detection and specificity
2Measurement precision
If conventional PSMA-targeted NIR dyes are used, then imaging capability is achieved, but skin clearance is slow leading to prolonged hospital stays
Solution Approach 1:
The patent optimizes pharmacokinetic parameters by modifying the molecular structure of NIR dyes, including changing spacer lengths and amino acid compositions. These changes accelerate renal clearance while preserving imaging capability, reducing the need for prolonged hospital stays
Solution Approach 2:
The patent designs NIR dyes with intentional short half-lives in non-target tissues, allowing rapid elimination from the body. This approach uses temporary imaging agents that fulfill their diagnostic purpose quickly and are then rapidly cleared, minimizing patient exposure time
3Quantity of substance
If PSMA-targeted ligands are conjugated to NIR dyes, then tumor accumulation is enhanced, but pharmacokinetic properties deteriorate
Solution Approach 1:
The patent introduces carefully designed linker molecules as intermediaries between PSMA-targeted ligands and NIR dyes. These linkers optimize the balance between tumor accumulation (by maintaining ligand affinity) and pharmacokinetic properties (by controlling solubility, stability, and clearance rates)
Solution Approach 2:
The patent applies different structural characteristics to different parts of the conjugate: the ligand portion is optimized for high PSMA binding affinity, the linker provides appropriate spacing and solubility, and the NIR dye ensures stable fluorescence. This local optimization of quality in each component achieves overall improved performance
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 solution provides PSMA-targeted NIR dyes with enhanced specificity, faster skin clearance, and improved tumor-to-background ratios, facilitating more effective imaging and surgery with reduced hospital stay and costs.
Implementation Method 1
PSMA-targeted ligands linked to NIR dyes... compounds for use in the targeted imaging of tumors expressing PSMA
Data Source
AI summary
The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for their therapeutic and diagnostic use. More specifically, this disclosure provides compounds and methods for diagnosing and treating diseases associated with cells and/or vasculature expressing prostate specific membrane antigen (PSMA), such as prostate cancer and related diseases. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.