{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:08Z","timestamp":1787027768501,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA280968"],"award-info":[{"award-number":["R01CA280968"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Positive surgical margins (PSMs) are a major predictor of recurrence in thyroid cancer; however, their intraoperative detection remains challenging, particularly for microscopic PSMs. This study aimed to demonstrate that a sprayable pH-sensitive near-infrared fluorescent probe (PH10) could specifically and robustly label thyroid tumors in orthotopic mouse models. The pH sensitivity, cytotoxicity, and cellular uptake mechanisms of PH10 were evaluated in papillary thyroid carcinoma (K1) and anaplastic thyroid carcinoma (8505C) cell lines in vitro. Orthotopic thyroid cancer mouse models were then established using both K1 and 8505C cells. In vivo fluorescence following topical spraying of PH10 was quantified after sequential washes to assess tumor-to-background ratios. Fluorescence-guided surgery (FGS) was performed to determine whether PH10 could facilitate complete resection of orthotopically grown thyroid tumors. Complete resection was validated by hematoxylin and eosin histology. PH10 demonstrated low cytotoxicity at clinically relevant concentrations in vitro and showed selective uptake into thyroid cancer cells, predominantly via organic anion transporting polypeptide-mediated transport. Topical spraying of PH10 in orthotopic thyroid cancer mouse models established from K1 and 8505C cell lines generated strong tumor-specific fluorescence. Tumor-to-background ratios were significantly higher than background and remained distinguishable after multiple washes. In both models, PH10 enabled visualization of macroscopic residual tumors and detection of microscopic PSMs, with fluorescence patterns closely corresponding to histologic findings. FGS enabled complete tumor resection, as confirmed by fluorescence and histology. In conclusion, topical application of PH10 provides rapid, tumor-specific fluorescence suitable for identifying PSMs and facilitating complete tumor resection by FGS in thyroid cancer.<\/jats:p>","DOI":"10.3390\/cancers18040632","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T14:09:54Z","timestamp":1771250994000},"page":"632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A pH-Sensitive Sprayable Fluorescent Probe Enables Accurate Visualization of Thyroid Cancer Margins for Fluorescence-Guided Surgery in Orthotopic Mouse Models"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-8749","authenticated-orcid":false,"given":"Hyungju","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Surgery, University of California San Diego, San Diego, CA 92092, USA"},{"name":"Department of Surgery, Ewha Womans University College of Medicine, Seoul 07985, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Bravo","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, San Diego, CA 92092, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Chun","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, San Diego, CA 92092, USA"},{"name":"Department of Surgery, National Taiwan University Hospital, Taipei 100225, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blackberrie","family":"Eddins","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, San Diego, CA 92092, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siamak","family":"Amirfakhri","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, San Diego, CA 92092, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Zaker","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, San Diego, CA 92092, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9177-2352","authenticated-orcid":false,"given":"Keita","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, San Diego, CA 92092, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Yokomizo","sequence":"additional","affiliation":[{"name":"Center for Inflammation Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0732-9779","authenticated-orcid":false,"given":"Homan","family":"Kang","sequence":"additional","affiliation":[{"name":"Center for Inflammation Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8018-5604","authenticated-orcid":false,"given":"Grace","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Diego, San Diego, CA 92092, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md","family":"Shamim","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7982-6483","authenticated-orcid":false,"given":"Hak Soo","family":"Choi","sequence":"additional","affiliation":[{"name":"Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, San Diego, CA 92092, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA 92161, USA"},{"name":"AntiCancer Inc., San Diego, CA 92111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8910-3257","authenticated-orcid":false,"given":"Satoshi","family":"Kashiwagi","sequence":"additional","affiliation":[{"name":"Center for Inflammation Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6475-0156","authenticated-orcid":false,"given":"Maged","family":"Henary","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0086-2159","authenticated-orcid":false,"given":"Michael","family":"Bouvet","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Diego, San Diego, CA 92092, 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