Small-Molecule Absorber A1094 as a Stable and Fast-Clearing NIR-II Imaging Agent

Area of Science:

• Biomedical Imaging
• Nanotechnology
• Medical Chemistry

Background:

• Photoacoustic imaging (PAI) in the second near-infrared window (NIR-II) enables deep-tissue visualization but often relies on exogenous agents.
• Current nanoparticle-based NIR-II agents face challenges with in vivo metabolism and clearance.
• Small-molecule agents offer potential advantages for clinical translation in PAI.

Purpose of the Study:

• To evaluate the small-molecule croconaine absorber A1094 (∼600 Da) as a novel NIR-II imaging agent for in vivo PAI.
• To assess the clinical translational potential of A1094, focusing on its solubility, stability, and clearance characteristics.
• To compare the performance of A1094 with gold nanorods (Au nanorods) in PAI of murine ears.

Main Methods:

• Systematic evaluation of A1094's in vivo properties, including solubility, blood circulation, stability (pH, redox, metabolic), and anti-interference.
• Intravenous administration of A1094 and Au nanorods in murine ear models for PAI.
• In vitro analysis using murine liver microsomes to identify A1094's metabolic pathways.

Main Results:

• A1094 demonstrated sufficient solubility, blood freeness, and favorable stability profiles.
• PAI of murine ears showed comparable capillary visibility with A1094 and Au nanorods, with significantly higher contrast enhancement for A1094 in healthy and inflamed tissues.
• A1094 exhibited significantly faster liver clearance (74.2% cleared in 3h) compared to Au nanorods (43.1% cleared in 3h).

Conclusions:

• A1094 is a promising small-molecule NIR-II imaging agent with good in vivo performance and stability.
• Its faster clearance profile compared to Au nanorods is advantageous for clinical applications.
• A1094 shows significant potential for clinical translation as a stable and rapidly cleared NIR-II PAI agent.