BF₂-Azadipyrromethene Fluorophores for Intraoperative Vital Structure Identification.

Area of Science:

• Organic Chemistry
• Biomedical Engineering
• Medical Imaging

Background:

• Fluorescence-guided surgery requires novel imaging agents emitting in the near-infrared (NIR) spectrum.
• Polyethylene glycol (PEG)-substituted BF2-azadipyrromethene fluorophores offer potential for NIR imaging.
• Optimizing PEGylation is crucial for enhancing aqueous fluorescence quantum yields and in vivo performance.

Purpose of the Study:

• To synthesize and characterize novel mono- and bis-PEGylated BF2-azadipyrromethene fluorophores for intraoperative fluorescence imaging.
• To evaluate the efficacy of these fluorophores for ureter imaging in preclinical rodent and porcine models.
• To assess the potential of these fluorophores for spectrally distinct tissue identification in surgical settings.

Main Methods:

• Synthesis of BF2-azadipyrromethene core structures with varying PEG chain lengths and conjugation (mono- vs. bis-).
• Characterization of photophysical properties, including fluorescence quantum yields in aqueous solutions.
• In vivo imaging studies in rodent and porcine models to assess renal excretion, ureteral visualization, and dose-dependency.
• 3-D emission heat map imaging to capture dynamic ureteral peristalsis.

Main Results:

• Bis-PEGylation significantly improved aqueous fluorescence quantum yields, with optimal PEG chain lengths between 2.9 and 4.6 kDa.
• Successful fluorescence-guided ureter identification was achieved in both rodent and porcine models.
• Doses of 0.1-0.5 mg/kg enabled sustained ureteral visualization for up to 120 minutes post-administration.
• 3-D imaging revealed dynamic changes in fluorescence intensity correlating with ureteral peristalsis.
• Fluorophore emission was spectrally distinct from indocyanine green, suggesting potential for multicolor imaging.

Conclusions:

• PEGylated BF2-azadipyrromethene fluorophores are effective agents for NIR fluorescence-guided ureter imaging.
• Optimized bis-PEGylation enhances water solubility and fluorescence properties for in vivo applications.
• These fluorophores demonstrate successful translation from rodent to porcine models, highlighting clinical potential.
• The distinct spectral properties open possibilities for combined use with existing clinical dyes for advanced intraoperative tissue differentiation.