PEGylated BF2-Azadipyrromethene (NIR-AZA) fluorophores, for intraoperative imaging
journal contributionposted on 15.11.2021, 17:15 authored by Dan WuDan Wu, Harrison C Daly, Emer Conroy, Bo Li, William M Gallagher, Ronan A Cahill, Donal O'SheaDonal O'Shea
Clinical imaging utilising near-infrared fluorescence is growing as an intraoperative aid for the decision-making processes during complex surgical procedures. Existing uses include perfusion assessment and lymph node identification with many new applications currently being proposed and developed. While imaging hardware and software have significantly progressed in recent times, suitable NIR-fluorophores remain a limiting factor. In this report, we describe the design, synthesis, photophysical characterization and in vivo imaging assessment of new PEGylated NIR-fluorophores based on the BF2-azadipyrromethene fluorophore class. The synthetic route includes PEGylation as the final step, thereby allowing routine access to derivatives substituted with different molecular weights of PEG. Absorption and emission wavelength maxima in PBS lie at 690 and 720 nm respectively with quantum yields over 12%. They show excellent photostability and no light induced singlet oxygen production. A time-course of NIR-fluorescence imaging, post i.v. administration, in BALB/c mice showed a rapid and preferential accumulation in the renal excretion pathway within 20 min, indicative of potential clinical usage for intraoperative identification of vial structures along this pathway. Assessment with clinical imaging equipment showed the NIR-AZA fluorophores to be wavelength compatible and brighter than currently used methylene blue (MB), and that they have the ability to be imaged simultaneously with indocyanine green (ICG) offering a potential for dual colour clinical imaging.
Science Foundation Ireland grant number 17/TIDA/4936
CommentsThe original article is available at https://www.sciencedirect.com
Published CitationWu D. et al. PEGylated BF2-Azadipyrromethene (NIR-AZA) fluorophores, for intraoperative imaging. Eur J Med Chem. 2019;161:343-353.
Publication Date19 October 2018
- Surgical Science and Practice
- Chemistry and Pharmaceutical Sciences
- Accepted Version (Postprint)
Cell Line, TumorMice, Inbred BALB CBreast NeoplasmsMammary Neoplasms, ExperimentalBoron CompoundsPolyethylene GlycolsAza CompoundsPorphobilinogenFluorescent DyesSpectrometry, FluorescenceMolecular StructureStructure-Activity RelationshipDose-Response Relationship, DrugOptical ImagingRenal EliminationFluorescence guided surgeryPEGylated NIR-FluorophoresMedicinal & Biomolecular ChemistryMedicinal and Biomolecular ChemistryPharmacology and Pharmaceutical Sciences