Dual Color Imaging from a Single BF2-Azadipyrromethene Fluorophore Demonstrated in vivo for Lymph Node Identification

Int J Med Sci. 2021 Feb 3;18(7):1541-1553. doi: 10.7150/ijms.52816. eCollection 2021.

Abstract

Dual emissions at ~700 and 800 nm have been achieved from a single NIR-AZA fluorophore 1 by establishing parameters in which it can exist in either its isolated molecular or aggregated states. Dual near infrared (NIR) fluorescence color lymph node (LN) mapping with 1 was achieved in a large-animal porcine model, with injection site, channels and nodes all detectable at both 700 and 800 nm using a preclinical open camera system. The fluorophore was also compatible with imaging using two clinical instruments for fluorescence guided surgery. Methods: An NIR-AZA fluorophore with hydrophilic and phobic features was synthesised in a straightforward manner and its aggregation properties characterised spectroscopically and by TEM imaging. Toxicity was assessed in a rodent model and dual color fluorescence imaging evaluated by lymph node mapping in a large animal porcine models and in ex-vivo human tissue specimen. Results: Dual color fluorescence imaging has been achieved in the highly complex biomedical scenario of lymph node mapping. Emissions at 700 and 800 nm can be achieved from a single fluorophore by establishing molecular and aggregate forms. Fluorophore was compatible with clinical systems for fluorescence guided surgery and no toxicity was observed in high dosage testing. Conclusion: A new, biomedical compatible form of NIR-dual emission wavelength imaging has been established using a readily accessible fluorophore with significant scope for clinical translation.

Keywords: J aggregate; NIR-AZA fluorophore; dual fluorescence; fluorescence-guided surgery; lymph node mapping..

MeSH terms

  • Animals
  • Endoscopy / instrumentation
  • Endoscopy / methods*
  • Female
  • Fluorescent Dyes / administration & dosage*
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / toxicity
  • HeLa Cells
  • Humans
  • Intraoperative Care / instrumentation
  • Intraoperative Care / methods
  • Intravital Microscopy / methods
  • Lymph Nodes / diagnostic imaging*
  • Lymphatic Metastasis / diagnosis
  • Male
  • Models, Animal
  • Neoplasms / pathology
  • Neoplasms / surgery
  • Optical Imaging / instrumentation
  • Optical Imaging / methods*
  • Porphobilinogen / administration & dosage
  • Porphobilinogen / analogs & derivatives
  • Porphobilinogen / chemistry
  • Porphobilinogen / toxicity
  • Rats
  • Spectrophotometry, Infrared / instrumentation
  • Spectrophotometry, Infrared / methods
  • Sus scrofa
  • Toxicity Tests, Subacute / methods

Substances

  • Fluorescent Dyes
  • dipyrromethene
  • Porphobilinogen