Highly Fluorinated Peptide Probes with Enhanced In Vivo Stability for ¹⁹ F-MRI

Area of Science:

• Biomedical Imaging
• Chemical Biology
• Materials Science

Background:

• ¹⁹ F-MRI offers unique advantages for in vivo imaging due to the absence of background signals.
• Developing effective contrast agents for ¹⁹ F-MRI requires high fluorine content and stability.
• Peptide-based probes are attractive due to their biocompatibility and tunable properties.

Purpose of the Study:

• To develop a novel labeling strategy for in vivo ¹⁹ F-MRI using highly fluorinated peptide probes.
• To create dual-purpose probes functionalized for bioconjugation and imaging.
• To assess the performance and stability of these probes in biological systems.

Main Methods:

• Synthesis of short, hydrophilic peptide probes incorporating perfluoro-tert-butyl groups for high fluorination.
• Utilizing d-amino acids and β-alanine to enhance probe stability and reduce cytotoxicity.
• Characterization of ¹⁹ F-NMR resonance properties and linewidth.
• In vivo imaging studies in zebrafish embryos and bioconjugation experiments.

Main Results:

• Developed peptide probes with high fluorine content (27 ¹⁹ F substitutions) and a single, narrow ¹⁹ F-NMR resonance (<10 Hz).
• Demonstrated successful in vivo ¹⁹ F-MRI performance with six distinct peptide probes.
• Observed high stability and long circulation times in zebrafish embryos via fluorescence microscopy.
• Showed successful bioconjugation to bovine serum albumin with a moderate increase in linewidth (≈30 Hz).

Conclusions:

• The developed peptide probes are highly suitable for in vivo ¹⁹ F-MRI.
• The labeling strategy provides a versatile platform for creating advanced imaging agents.
• These probes offer a promising tool for sensitive and specific biological imaging.