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Modular PET Agent Construction Strategy through Strain-Promoted Double-Click Reagent with Efficient Photoclick Step
Manshu Li1, Xinrui Ma1, Christopher J Molnar2
1Department of Radiology, Biomedical Research Imaging Center, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Bioconjugate Chemistry
|November 7, 2022
Summary
A new modular strategy enables rapid assembly of positron emission tomography (PET) agents using a sequential double-click reaction. This method efficiently links radioactive components with targeting molecules for improved imaging.
Area of Science:
- Radiochemistry
- Organic Synthesis
- Molecular Imaging
Background:
- Positron emission tomography (PET) imaging requires efficient synthesis of radiotracers.
- Current methods for PET agent assembly can be complex and time-consuming.
- Modularity in radiotracer design is crucial for optimizing pharmacokinetic properties.
Purpose of the Study:
- To develop an efficient and modular strategy for the rapid assembly of novel PET agents.
- To demonstrate a combinatorial approach for linking positron emitters with targeting ligands.
- To showcase the adaptability of the strategy for tuning agent properties.
Main Methods:
- Utilized a sequential, rapid, and selective double-click reaction strategy.
- Employed strain-promoted azide alkyne cyclization (SPAAC) for initial coupling.
- Incorporated a photocleavable protecting group on a cyclooctadiyne (MC-DIBOD) for sequential functionalization.
- Demonstrated modularity by modifying hydrophilicity of PSMA PET agents.
Main Results:
- Successfully assembled various PET agents using the developed modular strategy.
- The SPAAC reaction formed a stable intermediate with an 18F-labeled azide synthon.
- Photochemical deprotection of MC-DIBOD enabled subsequent azide-biomolecule conjugation.
- Modification of hydrophilicity in PSMA PET agents improved tumor-to-background contrast.
Conclusions:
- The developed modular strategy offers an efficient and rapid method for PET agent synthesis.
- The sequential click chemistry approach allows for combinatorial library generation.
- This strategy facilitates facile optimization of PET agents for enhanced diagnostic performance.
