Biomolecule Label Cleavage for Faster Radionuclide Clearance
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Solution Overview
Problem
Existing methods for clearing imaging or radiotherapy labels from biomolecules in vivo are inefficient, slow, and inconvenient, leading to high radiation doses and poor target-to-non-target ratios, which hamper effective imaging and therapy.
Innovation Solution
A compound comprising a label and an Administration Agent, administered in vivo, undergoes a bio-orthogonal reaction with a Cleaving Agent, such as a diene, to rapidly decouple the label from non-target sites, facilitating efficient clearance through the renal system.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If natural clearance methods are used to remove radionuclides from the body, then the process is safe and requires no additional agents, but the clearance is very slow leading to high radiation doses
Solution Approach 1:
The patent introduces a cleaving agent as an intermediary substance that reacts with the linker between the radionuclide and biomolecule, facilitating rapid cleavage and release of the radionuclide for quick excretion. This mediator enables controlled acceleration of the clearance process without direct harmful intervention.
Solution Approach 2:
The patent changes the chemical state of the linker by introducing a cleavable linkage that can be chemically modified by the cleaving agent. This parameter change transforms the stable radionuclide-biomolecule conjugate into separable components, enabling rapid radionuclide release and clearance from the body.
2Reliability
If antibodies are used as targeting agents, then high target uptake is achieved, but slow clearance from blood results in high radiation doses to bone marrow
Solution Approach 1:
The patent segments the antibody-radiometal conjugate into two separable parts through the cleavable linker: the antibody component that maintains target specificity and the radiometal component that can be rapidly cleared. This segmentation allows the antibody to fulfill its targeting function while enabling quick removal of the radioactive portion from circulation.
Solution Approach 2:
The patent extracts the radionuclide from the antibody conjugate at non-target sites through cleavage of the linker by the cleaving agent. This extraction removes the harmful radiation source from circulation while leaving the antibody intact at target sites, thereby reducing radiation exposure to sensitive tissues like bone marrow.
3Measurement precision
If imaging agents are administered, then target imaging is achieved, but circulating fractions of receptor capture agents before they reach target, negatively impacting target-background ratios
Solution Approach 1:
The patent applies preliminary action by administering the cleaving agent before or at the optimal time to cleave and remove circulating receptor fragments that would otherwise capture imaging agents. This preliminary clearance action prevents premature binding and ensures higher target-background ratios by reducing non-specific uptake in circulation.
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 method achieves rapid clearance of radionuclides from non-target tissues, significantly increasing target-to-non-target ratios and reducing radiation exposure, while maintaining therapeutic efficacy.
Implementation Method 1
A compound comprising a label and an Administration Agent, administered in vivo, undergoes a bio-orthogonal reaction with a Cleaving Agent, such as a diene, to rapidly decouple the label from non-target sites
Data Source
AI summary
Disclosed herein are compounds, combinations, and kits that can be used to more quickly remove radionuclides from a subject, preferably a human being. Said compounds, combinations and kits can also be used to increase the tumor-to-blood ratio, or to more rapidly and/or conveniently achieve such an increase, of a label in targeted imaging or targeted radiotherapy in a subject, preferably a human being.