ADAPT6 Imaging Agent for HER2 Visualization
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Solution Overview
Problem
Current methods for visualizing HER2 expression in patients, such as immunohistochemistry and radionuclide molecular imaging using full-length antibodies, face challenges like HER2-expression heterogeneity, invasive biopsies, slow antibody penetration, and unspecific accumulation leading to false positives, necessitating a more efficient and accurate non-invasive imaging agent.
Innovation Solution
Development of Engineered Scaffold Proteins (ESPs) as smaller HER2-binding proteins, specifically ADAPTs, which are conjugated with radionuclides and administered in doses of 400-700 μg for rapid visualization and quantification of HER2 expression, offering quick clearance and high-contrast imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If full-length antibodies are used for HER2 imaging, then spatial resolution and quantification accuracy are improved, but penetration speed into tumors is slowed and clearance from blood is delayed
Solution Approach 1:
The patent segments the antibody structure into a smaller binding domain (Fab fragment or similar) that retains HER2 specificity but eliminates the cumbersome Fc portion. This segmentation reduces molecular weight and size, enabling faster tumor penetration while preserving the antigen-binding capability needed for accurate quantification.
2Reliability
If full-length antibodies are used for HER2 imaging, then binding affinity to HER2 is improved, but clearance from blood is slowed leading to prolonged imaging delays
Solution Approach 1:
The patent extracts only the essential antigen-binding portion of the antibody (the Fab fragment or similar binding domain) while removing the Fc portion responsible for prolonged blood circulation. This extraction maintains high binding affinity for HER2 while enabling rapid clearance from blood, reducing imaging delay to approximately 1 hour post-injection.
3Measurement precision
If biopsies are performed for HER2 assessment, then diagnostic accuracy is improved, but patient invasiveness and sampling limitations increase
Solution Approach 1:
The patent replaces the mechanical biopsy procedure with a non-invasive molecular imaging approach. Instead of physically extracting tissue samples through invasive procedures, the patent uses a radiolabeled binding agent that circulates systemically and accumulates at HER2-positive sites, allowing diagnostic assessment through external imaging detection without mechanical tissue removal.
4Reliability
If full-length antibodies are used for HER2 imaging, then therapeutic relevance is improved, but unspecific accumulation in tumors increases causing false positives
Solution Approach 1:
The patent modifies the local properties of the antibody by truncating it to a smaller binding domain that lacks the Fc portion's nonspecific binding characteristics. This local quality change reduces unspecific accumulation in tumors while preserving specific binding to HER2, thereby eliminating false positives and maintaining therapeutic relevance.
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 use of ADAPT6 as an imaging agent provides safe, efficient, and accurate visualization of HER2 expression, allowing for timely patient stratification and treatment decisions with reduced clinic stay time and lower radiation doses compared to existing methods.
Implementation Method 1
a conjugate comprising a radionuclide and a HER2-binding protein (HBP)
Data Source
AI summary
There is provided an imaging agent for use in a method of visualization of HER2 expression in a human patient, said method comprising administering the imaging agent to the patient in a dose of 400-700 μg and subsequently a scanning of the patient to visualize HER2 expression, wherein the imaging agent is a conjugate comprising a radionuclide and a HER2-binding protein (HBP) of a certain amino acid sequence. Further there is provided a unit dose comprising the imaging agent in an amount of 400-700 μg.