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

Research Paper

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

Niamh Curtin1, Dan Wu1, Ronan Cahill2, Anwesha Sarkar2, Pól Mac Aonghusa3, Sergiy Zhuk3, Manuel Barberio4, Mahdi Al-Taher4, Jacques Marescaux5, Michele Diana4,5,6, Donal F. O'Shea1✉

1. Department of Chemistry, Royal College of Surgeons in Ireland, RCSI, 123 St Stephen's Green, Dublin 2, Ireland.
2. UCD Centre for Precision Surgery, School of Medicine, University College Dublin, Ireland; Department of Surgery, Mater Misericordiae University Hospital, Dublin, Ireland.
3. IBM Research - Ireland, Damastown Industrial Estate, Mulhuddart, Dublin 15, Ireland.
4. IHU-Strasbourg, Institute of Hybrid Image-Guided Surgery, Strasbourg, France.
5. IRCAD, Research Institute against Cancer of the Digestive System, Strasbourg, France.
6. ICube Lab, Photonics Instrumentation for Health, Strasbourg, France.

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Citation:
Curtin N, Wu D, Cahill R, Sarkar A, Aonghusa PM, Zhuk S, Barberio M, Al-Taher M, Marescaux J, Diana M, O'Shea DF. Dual Color Imaging from a Single BF2-Azadipyrromethene Fluorophore Demonstrated in vivo for Lymph Node Identification. Int J Med Sci 2021; 18(7):1541-1553. doi:10.7150/ijms.52816. Available from https://www.medsci.org/v18p1541.htm

File import instruction 2-Azadipyrromethene Fluorophore Demonstrated in vivo for Lymph Node Identification^~^2021^~^18^~^7^~^1541^~^1553^~^10.7150/ijms.52816^~^https://www.medsci.org/v18p1541.htm'>

Abstract

Graphic 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: NIR-AZA fluorophore, dual fluorescence, J aggregate, fluorescence-guided surgery, lymph node mapping.