Evidence map›Paper›PMID 42726450›Full record

ArticleMolecular diagnosis & therapy2026

Rapid Ex Vivo Visualization of Laryngeal Tumors Using a Sprayable pH-Activatable Fluorophore.

Daan G J Linders, Sebastiaan W R Dalmeijer, Bo E Zweedijk, Hamed Abbasi, Danielle Boldewijn, Sjors A Koppes, Bernd Kremer, Jacobus Burggraaf, Denise E Hilling, Joost R van der Vorst and 7 more

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Article in Molecular diagnosis & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

17 authors.

Daan G J Linders *Department of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.ORCID http://orcid.org/0000-0003-4524-4175
Sebastiaan W R Dalmeijer *Department of Surgery, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
Bo E ZweedijkDepartment of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Hamed AbbasiDepartment of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Danielle BoldewijnDepartment of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Sjors A KoppesDepartment of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Bernd KremerDepartment of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Jacobus BurggraafDepartment of Surgery, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
Denise E HillingDepartment of Surgery, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
Joost R van der VorstDepartment of Surgery, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
Jinhui SerGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Satoshi KashiwagiGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Maged HenaryDepartment of Chemistry, Center of Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA.
Jeroen C JansenDepartment of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
Alexander L VahrmeijerDepartment of Surgery, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
Hak Soo ChoiGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Stijn KeereweerDepartment of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands. s.keereweer@erasmusmc.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAchieving 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.

methodsFreshly 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.

resultsLaryngeal 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.

conclusionsThis 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.

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.