Peptide Liver Receptor Imaging Agent for Function Quantification
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Solution Overview
Problem
Current liver receptor imaging agents, such as Tc-99m-Galactosyl-Serum-Albumin, have high molecular weights and complex quality control procedures, and iodine labeling requires toxic oxidants, limiting their effectiveness and safety for quantifying remaining liver function and liver transplantation assessment.
Innovation Solution
A novel liver receptor imaging agent using a derivative of a single amino acid, lysine, polymerized with saccharide groups and labeled with In-111, Tc-99m, Ga-68, or Gd, without the need for oxidants, providing a safer and more efficient method for liver function quantification and targeting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If Tc-99m-Galactosyl-Serum-Albumin is used as a liver receptor imaging agent, then liver function quantification can be achieved, but the high molecular weight and complex quality control procedures reduce manufacturing ease and increase device complexity
Solution Approach 1:
The patent segments the imaging agent into a smaller peptide structure (YEE, YDD, or YEEE) rather than using the entire serum albumin protein. This segmentation reduces the molecular weight from 67 kD to 1-2 kD, simplifies quality control, and maintains the essential galactosamine groups needed for ASGPR binding while eliminating the manufacturing complexity of handling large proteins
Solution Approach 2:
The patent extracts only the essential functional components (galactosamine-containing peptide chains) from the serum albumin protein. By taking out the core binding functionality while removing the bulky protein structure, the invention creates a simplified agent that retains liver targeting capability but eliminates the quality control burdens associated with complex biological products
2Illumination intensity
If iodine labeling is used for liver receptor imaging agents, then imaging capability is achieved, but the requirement for toxic oxidants increases harmful factors and reduces safety
Solution Approach 1:
The patent changes the labeling parameter from iodine-based oxidation to direct chelation with metal isotopes (In-111, Tc-99m, Ga-68, or Gd). This parameter change eliminates the need for toxic oxidants like chloramine T, Iodobead, or Iodogen, while maintaining or enhancing imaging capability through alternative nuclear medicine approaches that do not require harmful chemical oxidation
Solution Approach 2:
The patent converts the limitation of avoiding iodine labeling (which would reduce imaging options) into a benefit by adopting metal isotope labeling. This alternative approach not only eliminates toxic oxidant exposure but also provides comparable or superior imaging capabilities through SPECT and PET modalities, turning a potential disadvantage into an advantage
3Adaptability or versatility
If large molecular weight proteins are used as imaging agents, then liver targeting capability is achieved, but the position and number of saccharide groups and DTPA cannot be determined exactly, increasing device complexity
Solution Approach 1:
The patent segments the large protein structure into small, well-defined peptide chains (YEE, YDD, YEEE) with known sequences and structures. This segmentation allows precise determination of saccharide group positions and DTPA attachment sites through mass spectrometry, eliminating the structural characterization complexity inherent in large proteins while preserving liver targeting through retained ASGPR-binding galactosamine groups
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 new agent effectively quantifies remaining liver function, reduces toxicity, and enhances the accuracy of liver transplantation decisions by achieving high binding strength with liver receptors and efficient liver targeting, as demonstrated by SPECT/CT imaging and bio-distribution studies.
Implementation Method 1
After binding with ASGPR, glycopeptides or glycoproteins with Gal and GalNAc end enter hepatocytes through receptor-mediated endocytosis
Implementation Method 2
A liver receptor imaging agent is intravenously injected as agent, and then the radioactivity per square unit in liver is quantified by SPECT/CT image quantitative analysis
Data Source
AI summary
A test indicator for quantifying remaining liver function is provided. A novel liver receptor imaging agent with liver targeting property is utilized to develop a method for quantifying remaining liver function to serve as test indicator for judging the liver failure outcome in clinic, particularly for judging the necessity of liver transplantation for patients with liver failure or liver disease. The radioactivity uptake of the test indicator was negatively correlated with the extent of liver reserve. The cutoff value of liver reserve for liver transplantation is also disclosed.