Development and Validation of Nerve-Targeted Bacteriochlorin Sensors

Area of Science:

• Porphyrin chemistry
• Bio-imaging probes
• Molecular imaging agents

Background:

• Bacteriochlorins (bacs) are near-infrared probes for multimodal imaging.
• Existing bacs have limitations in biomolecule labeling, chemical purity, and solubility.
• These limitations hinder their application in sensitive bio-imaging.

Purpose of the Study:

• To develop novel bacteriochlorins (bacs) with enhanced properties for targeted bio-imaging.
• To improve the chemical stability, clickability, and solubility of bacs.
• To demonstrate the utility of functionalized bacs for preclinical nerve imaging.

Main Methods:

• Synthesis of bacteriochlorins (bacs) via trimolecular cycloaddition.
• Functionalization of bacs with clickable linkers for biomolecule conjugation.
• Labeling of bacs with Hs1a peptide for targeted nerve delivery.
• In vivo imaging using fluorescent and radiolabeled bac probes.

Main Results:

• Novel bacs with improved stability, clickability, and solubility were synthesized.
• Bac-Hs1a and radiolabeled Hs1a successfully targeted peripheral nerves in mice.
• High signal-to-background ratios were observed in fluorescence, Cerenkov luminescence, and PET/CT imaging.
• Demonstrated accumulation of probes in peripheral nerves for enhanced contrast.

Conclusions:

• The developed bac probes offer a modular platform for advanced bio-imaging.
• Functionalized bacs show significant potential for preclinical diagnosis and multiplex nerve imaging.
• This work provides a foundation for the development of novel diagnostic and imaging agents.