{
  "abstract": "Introduction: Achieving clear resection margins (> 5 mm) is critical during laryngeal and hypopharyngeal tumor resection, as positive margins are associated with reduced disease-specific survival. Near-infrared (NIR) fluorescence imaging has emerged as a valuable tool for intraoperative margin assessment by enabling real-time visualization of residual tumor tissue. However, current fluorescent contrast agents rely on intravenous administration, often requiring dosing hours to days before surgery. Also, targeting tumor-specific biomarkers with heterogeneous expression limits applicability. To address these limitations, we evaluated the feasibility of a topically applied pH-activatable fluorophore (PH10), which selectively fluoresces under acidic conditions. This ex vivo proof-of-concept study investigates whether topical PH10 can visualize laryngeal and hypopharyngeal tumors.\n\nMethods: Freshly resected laryngeal and hypopharyngeal squamous cell carcinoma (SCC) specimens were obtained from ten patients and topically sprayed with PH10 immediately after surgery. Following a 2-min incubation period, NIR fluorescence images were acquired before and after three sequential saline washes. Fluorescence intensity was quantified as the tumor-to-background ratio (TBR); tumor localization was confirmed on histopathology.\n\nResults: Laryngeal tumors demonstrated tumor-specific fluorescence upon PH10 application, with significantly higher signal intensity in tumor tissue compared to adjacent normal mucosa (P < 0.05). The median TBR after the first wash was 2.3 (interquartile range 1.7–3.0), exceeding the clinically relevant threshold of 1.5 in seven of seven laryngeal SCC cases; however, this threshold was not reached in either of the two hypopharyngeal carcinoma cases included.\n\nConclusions: This proof-of-concept study suggests that PH10, a sprayable pH-activatable fluorophore, can enable rapid and high-contrast visualization of laryngeal tumors, although this was not observed in the small number of hypopharyngeal cases evaluated. Given its topical application and rapid activation, PH10 may hold promise for intraoperative margin assessment, yet these preliminary findings, based on a small and heterogeneous sample, require validation in larger cohorts, including direct correlation with deep resection margins, before clinical utility can be established.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands",
    "Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands",
    "Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands",
    "Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands",
    "Centre for Human Drug Research, 2333 AL Leiden, The Netherlands",
    "Leiden Academic Center for Drug Research, Leiden University, 2300 RA Leiden, The Netherlands",
    "Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands",
    "Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 USA",
    "Center for Inflammation Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 USA",
    "Department of Chemistry, Center of Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303 USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Daan G. J. Linders",
      "orcid": "0000-0003-4524-4175"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Sebastiaan W. R. Dalmeijer"
    },
    {
      "affs": [
        2
      ],
      "name": "Bo E. Zweedijk"
    },
    {
      "affs": [
        2
      ],
      "name": "Hamed Abbasi"
    },
    {
      "affs": [
        2
      ],
      "name": "Danielle Boldewijn"
    },
    {
      "affs": [
        3
      ],
      "name": "Sjors A. Koppes"
    },
    {
      "affs": [
        2
      ],
      "name": "Bernd Kremer"
    },
    {
      "affs": [
        1,
        4,
        5
      ],
      "name": "Jacobus Burggraaf"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Denise E. Hilling"
    },
    {
      "affs": [
        1
      ],
      "name": "Joost R. van der Vorst"
    },
    {
      "affs": [
        7
      ],
      "name": "Jinhui Ser"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Satoshi Kashiwagi"
    },
    {
      "affs": [
        9
      ],
      "name": "Maged Henary"
    },
    {
      "affs": [
        0
      ],
      "name": "Jeroen C. Jansen"
    },
    {
      "affs": [
        1
      ],
      "name": "Alexander L. Vahrmeijer"
    },
    {
      "affs": [
        7
      ],
      "name": "Hak Soo Choi"
    },
    {
      "affs": [
        2
      ],
      "name": "Stijn Keereweer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8wg5dpjzrzx8h.bib",
  "cited_by": 0,
  "doi": "10.1007/s40291-026-00878-x",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710600/",
  "id": "8wg5dpjzrzx8h",
  "issns": [
    "1177-1062",
    "1179-2000"
  ],
  "landing_url": "https://doi.org/10.1007/s40291-026-00878-x",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research Article"
    ],
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      "openalex",
      "2741|Optical Imaging and Spectroscopy Techniques"
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  "openalex": "W7212219905",
  "pdf_url": "https://link.springer.com/content/pdf/10.1007/s40291-026-00878-x.pdf",
  "pmcid": "PMC13710600",
  "pmid": "42726450",
  "published": "2026-09-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8wg5dpjzrzx8h.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:32Z",
      "native_id": "PMC13710600",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s40291-026-00878-x"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Optical Imaging and Spectroscopy Techniques",
      "subfield": "imaging"
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  ],
  "title": "Rapid Ex Vivo Visualization of Laryngeal Tumors Using a Sprayable pH-Activatable Fluorophore",
  "title_text": "Rapid Ex Vivo Visualization of Laryngeal Tumors Using a Sprayable pH-Activatable Fluorophore",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:32Z",
  "url": "https://research.draconitic.com/paper/8wg5dpjzrzx8h",
  "venue": "Molecular Diagnosis & Therapy",
  "versions": []
}