Enzymatically Catalyzed Radiofluorination of Biomolecules

Area of Science:

• Biochemistry
• Radiochemistry
• Molecular Imaging

Background:

• Amino acid-based molecular imaging agents, including peptides and proteins, are rapidly advancing.
• Fluorine-18 (half-life: 109.7 min) is a positron-emitting isotope well-suited for small molecular constructs in imaging.
• Existing indirect fluorine-18 labeling methods have limited clinical translation.

Purpose of the Study:

• To present methods for preparing two novel [18F]fluorocarboxylates.
• To demonstrate the enzymatic ligation of these [18F]fluorocarboxylates to a peptide sequence (LAP peptide).
• To explore a mild, site-specific radiofluorination approach using lipoic acid ligase.

Main Methods:

• Preparation of two distinct fluorine-18 labeled carboxylate substrates.
• Enzymatic radiofluorination using lipoic acid ligase for site-specific conjugation.
• Ligation of the [18F]fluorocarboxylates to a LAP peptide sequence.

Main Results:

• Successful synthesis of two [18F]fluorocarboxylate precursors.
• Demonstration of enzymatic coupling of [18F]fluorocarboxylates to the LAP peptide.
• Validation of a mild and site-specific radiofluorination strategy.

Conclusions:

• Enzymatic radiofluorination using lipoic acid ligase is a promising method for developing novel fluorine-18 imaging agents.
• This approach facilitates site-specific labeling of biomolecules with 18F-labeled carboxylates.
• Further development could advance the clinical application of these molecular imaging agents.