{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:53:38Z","timestamp":1767837218406,"version":"3.49.0"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T00:00:00Z","timestamp":1677283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Irish Government Department of Business, Enterprise and Innovation\u2019s Disruptive Technology Innovation Fund","award":["17\/TIDA\/4936"],"award-info":[{"award-number":["17\/TIDA\/4936"]}]},{"name":"Irish Government Department of Business, Enterprise and Innovation\u2019s Disruptive Technology Innovation Fund","award":["18\/RI\/5759"],"award-info":[{"award-number":["18\/RI\/5759"]}]},{"name":"Irish Government Department of Business, Enterprise and Innovation\u2019s Disruptive Technology Innovation Fund","award":["12\/RC\/2275_P2"],"award-info":[{"award-number":["12\/RC\/2275_P2"]}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["17\/TIDA\/4936"],"award-info":[{"award-number":["17\/TIDA\/4936"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["18\/RI\/5759"],"award-info":[{"award-number":["18\/RI\/5759"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["12\/RC\/2275_P2"],"award-info":[{"award-number":["12\/RC\/2275_P2"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Synthesis and Solid State Pharmaceutical Centre (SSPC)","doi-asserted-by":"publisher","award":["17\/TIDA\/4936"],"award-info":[{"award-number":["17\/TIDA\/4936"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Synthesis and Solid State Pharmaceutical Centre (SSPC)","doi-asserted-by":"publisher","award":["18\/RI\/5759"],"award-info":[{"award-number":["18\/RI\/5759"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Synthesis and Solid State Pharmaceutical Centre (SSPC)","doi-asserted-by":"publisher","award":["12\/RC\/2275_P2"],"award-info":[{"award-number":["12\/RC\/2275_P2"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ARC Foundation","award":["17\/TIDA\/4936"],"award-info":[{"award-number":["17\/TIDA\/4936"]}]},{"name":"ARC Foundation","award":["18\/RI\/5759"],"award-info":[{"award-number":["18\/RI\/5759"]}]},{"name":"ARC Foundation","award":["12\/RC\/2275_P2"],"award-info":[{"award-number":["12\/RC\/2275_P2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A series of mono- and bis-polyethylene glycol (PEG)-substituted BF2-azadipyrromethene fluorophores have been synthesized with emissions in the near-infrared region (700\u2013800 nm) for the purpose of fluorescence guided intraoperative imaging; chiefly ureter imaging. The Bis-PEGylation of fluorophores resulted in higher aqueous fluorescence quantum yields, with PEG chain lengths of 2.9 to 4.6 kDa being optimal. Fluorescence ureter identification was possible in a rodent model with the preference for renal excretion notable through comparative fluorescence intensities from the ureters, kidneys and liver. Ureteral identification was also successfully performed in a larger animal porcine model under abdominal surgical conditions. Three tested doses of 0.5, 0.25 and 0.1 mg\/kg all successfully identified fluorescent ureters within 20 min of administration which was sustained up to 120 min. 3-D emission heat map imaging allowed the spatial and temporal changes in intensity due to the distinctive peristaltic waves of urine being transferred from the kidneys to the bladder to be identified. As the emission of these fluorophores could be spectrally distinguished from the clinically-used perfusion dye indocyanine green, it is envisaged that their combined use could be a step towards intraoperative colour coding of different tissues.<\/jats:p>","DOI":"10.3390\/molecules28052167","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T02:10:46Z","timestamp":1677463846000},"page":"2167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["BF2-Azadipyrromethene Fluorophores for Intraoperative Vital Structure Identification"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5844-5868","authenticated-orcid":false,"given":"Cathal","family":"Caulfield","sequence":"first","affiliation":[{"name":"Department of Chemistry, Royal College of Surgeons in Ireland (RCSI), D02 PN40 Dublin 2, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Royal College of Surgeons in Ireland (RCSI), D02 PN40 Dublin 2, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2118-6345","authenticated-orcid":false,"given":"Ian S.","family":"Miller","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland (RCSI), D02 PN40 Dublin 2, Ireland"},{"name":"National Pre-clinical Imaging Centre (NPIC), Royal College of Surgeons in Ireland (RCSI), D02 PN40 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette T.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland (RCSI), D02 PN40 Dublin 2, Ireland"},{"name":"National Pre-clinical Imaging Centre (NPIC), Royal College of Surgeons in Ireland (RCSI), D02 PN40 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00f3l","family":"Mac Aonghusa","sequence":"additional","affiliation":[{"name":"IBM Research-Ireland, Damastown Industrial Estate, Mulhuddart, D02 PN40 Dublin 15, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergiy","family":"Zhuk","sequence":"additional","affiliation":[{"name":"IBM Research-Ireland, Damastown Industrial Estate, Mulhuddart, D02 PN40 Dublin 15, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2186-9421","authenticated-orcid":false,"given":"Lorenzo","family":"Cinelli","sequence":"additional","affiliation":[{"name":"Research Institute against Digestive Cancer (IRCAD), 67000 Strasbourg, France"},{"name":"Department of Gastrointestinal Surgery, San Raffaele Hospital IRCCS, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5393-6783","authenticated-orcid":false,"given":"Elisa","family":"Bannone","sequence":"additional","affiliation":[{"name":"Research Institute against Digestive Cancer (IRCAD), 67000 Strasbourg, France"},{"name":"Department of Surgery, Istituto Fondazione Poliambulanza, 25124 Brescia, Italy"},{"name":"Department of Pancreatic Surgery, Verona University, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1400-6230","authenticated-orcid":false,"given":"Jacques","family":"Marescaux","sequence":"additional","affiliation":[{"name":"Research Institute against Digestive Cancer (IRCAD), 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvain","family":"Gioux","sequence":"additional","affiliation":[{"name":"ICube Lab, Photonics Instrumentation for Health, 67400 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1390-8486","authenticated-orcid":false,"given":"Michele","family":"Diana","sequence":"additional","affiliation":[{"name":"Research Institute against Digestive Cancer (IRCAD), 67000 Strasbourg, France"},{"name":"ICube Lab, Photonics Instrumentation for Health, 67400 Strasbourg, France"},{"name":"Digestive and Endocrine Surgery, Nouvel Hospital Civil, University of Strasbourg, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taryn L.","family":"March","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander L.","family":"Vahrmeijer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1270-4000","authenticated-orcid":false,"given":"Ronan","family":"Cahill","sequence":"additional","affiliation":[{"name":"UCD Centre for Precision Surgery, School of Medicine, University College Dublin, D02 PN40 Dublin 4, Ireland"},{"name":"Department of Surgery, Mater Misericordiae University Hospital, D02 PN40 Dublin 7, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donal F.","family":"O\u2019Shea","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Royal College of Surgeons in Ireland (RCSI), D02 PN40 Dublin 2, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41571-021-00548-3","article-title":"Fundamentals and developments in fluorescence-guided cancer surgery","volume":"19","author":"Mieog","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"042002","DOI":"10.1088\/2050-6120\/ac1dbb","article-title":"Fluorescence-guided surgery","volume":"9","author":"Stewart","year":"2021","journal-title":"Methods Appl. Fluoresc."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Van Keulen, S., Hom, M., White, H., Rosenthal, E.L., and Baik, F.M. (2022). The evolution of fluorescence-guided surgery. Mol. Imaging Biol.","DOI":"10.1007\/s11307-022-01772-8"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"314","DOI":"10.3389\/fonc.2017.00314","article-title":"Fluorescence-guided surgery","volume":"7","author":"Nagaya","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1186\/s12951-022-01648-7","article-title":"In vivo fluorescence imaging: Success in preclinical imaging paves the way for clinical applications","volume":"20","author":"Refaat","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"895","DOI":"10.2147\/IJWH.S330060","article-title":"A review on the etiology, prevention, and management of ureteral injuries during obstetric and gynecologic surgeries","volume":"13","author":"Tijani","year":"2021","journal-title":"Int. J. Womens Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1177\/1756287214526767","article-title":"Management of iatrogenic ureteral injury","volume":"6","author":"Burks","year":"2014","journal-title":"Ther. Adv. Urol."},{"key":"ref_8","first-page":"31","article-title":"Ureteric injury during gynaecological surgery\u2014Lessons from 20 cases in Canada","volume":"12","author":"Jacob","year":"2020","journal-title":"Facts Views Vis. Obgyn."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.juro.2017.12.067","article-title":"Complications of recognized and unrecognized iatrogenic ureteral injury at time of hysterectomy: A population based analysis","volume":"199","author":"Blackwell","year":"2018","journal-title":"J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shoupe, D. (2017). Handbook of Gynecology, Springer.","DOI":"10.1007\/978-3-319-17798-4"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e190","DOI":"10.1097\/AS9.0000000000000190","article-title":"Indocyanine green fluorescence-guided surgery for gastrointestinal tumors: A systematic review","volume":"3","author":"Sposito","year":"2022","journal-title":"Ann. Surg. Open."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6374","DOI":"10.3748\/wjg.v27.i38.6374","article-title":"Intraoperative use of indocyanine green fluorescence imaging in rectal cancer surgery: The state of the art","volume":"27","author":"Peltrini","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s10151-017-1731-8","article-title":"Intraoperative use of ICG fluorescence imaging to reduce the risk of anastomotic leakage in colorectal surgery: A systematic review and meta-analysis","volume":"22","year":"2018","journal-title":"Tech. Coloproctol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.transproceed.2006.01.049","article-title":"Plasma disappearance rate of indocyanine green in liver dysfunction","volume":"38","author":"Faybik","year":"2006","journal-title":"Transplant. Proc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1172\/JCI104072","article-title":"Indocyanine green: Observations on its physical properties, plasma decay and hepatic extraction","volume":"39","author":"Cherrick","year":"1960","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4","DOI":"10.21037\/ls-20-111","article-title":"A systematic review of clinically available and experimental dyes for intraoperative near-infrared fluorescence imaging of the ureters during laparoscopic surgery","volume":"5","author":"Faber","year":"2021","journal-title":"Laparosc. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.7150\/thno.71359","article-title":"Activatable NIR-II organic fluorescent probes for bioimaging","volume":"12","author":"Zhang","year":"2022","journal-title":"Theranostics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1089\/lap.2020.0491","article-title":"The use of IRDye 800BK for intraoperative ureteral visualization: The future of the ureter is bright!","volume":"30","author":"Diana","year":"2020","journal-title":"J. Laparoendosc. Adv. Surg. Tech."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mahalingam, S.M., Putt, K.S., Srinivasarao, M., and Low, P.S. (2021). Design of a near infrared fluorescent ureter imaging agent for prevention of ureter damage during abdominal surgeries. Molecules., 26.","DOI":"10.3390\/molecules26123739"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7533","DOI":"10.1039\/D0CS00234H","article-title":"Bio applications of small molecule Aza-BODIPY: From rational structural design to in vivo investigations","volume":"49","author":"Shi","year":"2020","journal-title":"Chem. Soc. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"35655","DOI":"10.1039\/D2RA06534G","article-title":"Exploiting directed self-assembly and disassembly for off-to-on fluorescence responsive live cell imaging","volume":"12","author":"Curtin","year":"2022","journal-title":"RSC Adv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2165\/00063030-200822050-00004","article-title":"The impact of PEGylation on biological therapies","volume":"22","author":"Veronese","year":"2008","journal-title":"Biodrugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.ejmech.2017.04.051","article-title":"BF2-azadipyrromethene NIR-emissive fluorophores with research and clinical potential","volume":"135","author":"Daly","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s11705-019-1828-x","article-title":"Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF2 azadipyrromethene fluorophores","volume":"14","author":"Wu","year":"2020","journal-title":"Front. Chem. Sci. Eng."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.7150\/thno.42702","article-title":"An EPR strategy for bio-responsive fluorescence guided surgery with simulation of the benefit for imaging","volume":"10","author":"Daly","year":"2020","journal-title":"Theranostics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15657","DOI":"10.1021\/acsomega.0c01869","article-title":"Effect of short PEG on near-infrared BODIPY-based activatable optical probes","volume":"5","author":"Inagaki","year":"2020","journal-title":"ACS Omega"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1021\/acs.bioconjchem.8b00820","article-title":"Activatable near-infrared fluorescence imaging using PEGylated bacteriochlorin-based chlroin and BODIPY-dyads as probes for detecting cancer","volume":"30","author":"Ogata","year":"2019","journal-title":"Bioconjug. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14034","DOI":"10.1021\/jp2077775","article-title":"BF2-azadipyrromethenes: Probing the excited-state dynamics of a NIR fluorophore and photodynamic therapy agent","volume":"115","author":"Batat","year":"2011","journal-title":"J. Phys. Chem. A"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5386","DOI":"10.1021\/ol902140v","article-title":"Azide conjugatable and pH responsive near-infrared fluorescent imaging probes","volume":"11","author":"Murtagh","year":"2009","journal-title":"Org. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4468","DOI":"10.1016\/j.tetlet.2017.10.034","article-title":"Comparative triad of routes to an alkyne-BF2 azadipyrromethene near-infrared fluorochrome","volume":"58","author":"Wu","year":"2017","journal-title":"Tet. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ejmech.2018.10.046","article-title":"PEGylated BF2-azadipyrromethene (NIR-AZA) fluorophores, for intraoperative imaging","volume":"161","author":"Wu","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.1364\/BOE.5.002726","article-title":"Measurements of extrinsic fluorescence in intralipid and polystyrene microspheres","volume":"5","author":"Nie","year":"2014","journal-title":"Biomed. Opt. Express."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"080901","DOI":"10.1117\/1.JBO.21.8.080901","article-title":"Review of fluorescence guided surgery systems: Identification of key performance capabilities beyond indocyanine green imaging","volume":"21","author":"DSouza","year":"2016","journal-title":"J. Biomed. Opt."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1364\/OL.42.002964","article-title":"Multispectral open-air intraoperative fluorescence imaging","volume":"42","author":"Behrooz","year":"2017","journal-title":"Opt. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4501","DOI":"10.1038\/s41598-021-84121-z","article-title":"Intraoperative ureter identification with a novel fluorescent catheter","volume":"11","author":"Barberio","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.7150\/ijms.52816","article-title":"Dual color imaging from a single BF2-azadipyrromethene fluorophore demonstrated in vivo for lymph node identification","volume":"18","author":"Curtin","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_37","unstructured":"(2023, February 24). Python Programs Used, Together with Supporting Data, Are Available for Download at Github. Available online: https:\/\/github.com\/pol-maca\/icg-imaging."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/jgm.1473","article-title":"Animal research: Reporting in vivo experiments: The ARRIVE guidelines","volume":"12","author":"Kilkenny","year":"2010","journal-title":"J. Gene Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/5\/2167\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:42:42Z","timestamp":1760121762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/5\/2167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,25]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["molecules28052167"],"URL":"https:\/\/doi.org\/10.3390\/molecules28052167","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,25]]}}}