"Click labeling" with 2-[18f]fluoroethylazide for positron emission tomography

Area of Science:

• Radiochemistry
• Organic Chemistry
• Bioconjugation

Background:

• Development of novel radiolabeling strategies is crucial for advancing molecular imaging and targeted therapies.
• Fluorine-18 (18F) is a key positron-emitting isotope for Positron Emission Tomography (PET) imaging.
• Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), or click chemistry, offers high efficiency and selectivity for bioconjugation.

Purpose of the Study:

• To explore the utility of the Cu(I)-catalyzed Huisgen cycloaddition for the synthesis of 18F-labeled 1,2,3-triazoles.
• To develop a flexible and efficient method for incorporating 18F into complex molecules, including peptides.
• To optimize reaction conditions for rapid and high-yield 18F-labeling.

Main Methods:

• Synthesis of 2-[(18)F]fluoroethylazide via nucleophilic fluorination and distillation.
• Reaction of 2-[(18)F]fluoroethylazide with a library of terminal alkynes using Cu(2+)/ascorbate or copper powder catalysis.
• Radiolabeling of a model peptide using the optimized click reaction conditions.

Main Results:

• 2-[(18)F]fluoroethylazide was prepared in 55% radiochemical yield.
• High yields of 18F-labeled 1,2,3-triazoles were achieved with various terminal alkynes, with N-benzylpropynamide showing near-quantitative incorporation.
• A model peptide was successfully radiolabeled with 18F, yielding 92.3% radiochemical yield after purification.

Conclusions:

• The Cu(I)-catalyzed click reaction provides a versatile and efficient method for synthesizing 18F-labeled 1,2,3-triazoles.
• This methodology is suitable for the late-stage radiolabeling of biomolecules, such as peptides, with 18F.
• The developed approach enhances flexibility in 18F-labeling chemistry for PET imaging applications.