4.5 Article

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

Journal

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
Volume 18, Issue 7, Pages 1541-1553

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/ijms.52816

Keywords

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

Funding

  1. Irish Government Department of Business, Enterprise and Innovation's Disruptive Technology Innovation Fund
  2. Science Foundation Ireland [17/TIDA/4936]
  3. ARC Foundation
  4. AMBER [12/RC/2278 P2]
  5. Science Foundation Ireland (SFI) [17/TIDA/4936] Funding Source: Science Foundation Ireland (SFI)

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Dual emissions at around 700 and 800 nm have been achieved from a single fluorophore, allowing for successful lymph node mapping in a large animal model. The synthesized fluorophore with hydrophilic and phobic features was non-toxic and compatible with clinical systems.
Dual emissions at similar to 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.

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