Dual-Mode 18F-Labelled Compounds Using BF3 Exchange for Theranostics
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Solution Overview
Problem
Current PET imaging and radiotherapy practices face challenges due to the use of different radiometals for imaging and therapy, leading to variations in uptake and affinity, making it difficult to correlate images and predict radiotherapeutic uptake, and there is a need for theranostic dual-function PET imaging tracers/radiotherapeutics for improved treatment planning.
Innovation Solution
Development of dual-mode compounds comprising a metal chelator and a trifluoroborate moiety for 18F/19F exchange, allowing for both imaging and therapy using the same isotope, with cell-targeting domains such as peptides or antibodies, and the use of linkers like Lys(AMBF3) for chelation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If different radiometals are used for imaging and therapy, then imaging and therapy can be performed, but uptake and affinity vary making it difficult to correlate images and predict radiotherapeutic uptake
Solution Approach 1:
The patent creates a universal peptide compound that can be labeled with different radiometals (e.g., 18F for imaging, 90Y for therapy) while maintaining consistent biological behavior. The peptide backbone and chelator configuration remain unchanged, ensuring that the same molecular structure binds to the target with consistent affinity regardless of which radiometal is used, thereby enabling reliable correlation between imaging and therapy predictions.
2Ease of manufacture
If 18F-fluoride is used for labeling, then scalability and cost are improved, but the short half-life challenges peptide labeling
Solution Approach 1:
The patent incorporates the trifluoroborate group into the peptide structure during synthesis before radiolabeling. This pre-installation of the reactive BF3 group allows for rapid and efficient 18F labeling via simple fluorination reaction, overcoming the time constraints imposed by the short 18F half-life. The peptide is ready for immediate labeling without requiring complex post-synthesis conjugation steps.
3Ease of operation
If radiometal chelation is used for labeling, then ease of labeling is achieved, but cost increases and scalability decreases
Solution Approach 1:
The patent replaces expensive radiometal chelation chemistry with a cheaper, more scalable fluorination approach using 18F-fluoride. Instead of using complex metal chelators that require specialized reagents and procedures, the method uses simple BF3-containing moieties that can be readily fluorinated with commercially available 18F-fluoride, significantly reducing material costs and improving manufacturing scalability while maintaining labeling efficiency.
4Adaptability or versatility
If different metals are used for imaging and therapy, then imaging and therapy can be performed, but there are only a few instances where two metal isotopes can be identified to provide for a theranostic pair
Solution Approach 1:
The patent creates a universal peptide platform that can accommodate multiple radiometals including 18F, 68Ga, 64Cu, 90Y, and 177Lu. The same peptide backbone with appropriate chelators can be labeled with any of these metals, enabling theranostic pairs such as 18F/90Y, 68Ga/90Y, and 64Cu/177Lu. This universality overcomes the limitation of few available theranostic pairs by providing a single compound platform that supports multiple metal isotope combinations.
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
Enables accurate PET imaging followed by targeted therapy with the same compound, improving treatment planning and efficacy by ensuring consistent uptake and affinity, reducing the need for separate imaging and therapeutic agents.
Implementation Method 1
a trifluoroborate (BF3)-containing moiety configured for 19F/18F exchange or a boronate prescursor that is capable of conversion to an 18F-labeled trifluoroborate
Implementation Method 2
a metal chelator configured for chelation with a radioactive metal isotope or a non-radioactive metal isotope
Implementation Method 3
18F-fluoride offers scalability at lower cost. Thus 18F-fluoride is preferred: it decays cleanly (>97% β+)
Data Source
AI summary
A compound or molecular complex. The compound or molecular complex comprises: a metal chelator configured for chelation with a radioactive isotope or a non-radioactive isotope; and a trifluoroborate (BF3)-containing moiety configured for 19F/18F exchange or a precursor thereof; and optionally a cell-targeting domain.