Visualizing the distribution of durvalumab targeting PD-L1 using quantitative fluorescence imaging in patients with esophageal cancer.
9 affiliations
- 1Department of Gastroenterology and Hepatology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
- 2Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
- 3Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
- 4Department of Medical Oncology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
- 5Department of Gastroenterology and Hepatology, Martini Hospital, Groningen, Van Swietenplein 1, 9728 NT Groningen, The Netherlands.
- 6Department of Radiation Oncology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
- 7Department of Surgery, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
- 8Early Cancer Institute, Department of Oncology, University of Cambridge, Adrian Way, Cambridge CB2 0XZ, United Kingdom.
- 9Department of Otorhinolaryngology, Head and Neck Surgery, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Abstract
Rationale
Immune checkpoint inhibition (ICI) targeting programmed death-1 or its ligand (PD-1/PD-L1) is being explored as an addition to standard treatment for esophageal cancer (EC) to improve response rates, yet robust methods for patient selection are lacking. The predictive value of PD-L1 expression in biopsies is inconsistent due to intra- and intertumoral heterogeneity, and the impact of neoadjuvant chemoradiotherapy (CRT) on ICI response is unclear. Improving patient selection for receiving ICI therapies in patients with EC requires a better understanding of the drug's distribution and target binding. Here, we investigated the distribution of fluorescently labelled durvalumab (durvalumab-680LT) using ultrasound-guided quantitative fluorescence molecular endoscopy (US-qFME) before and after CRT in 20 patients with EC.Methods
US-qFME included in vivo mucosal fluorescence imaging, spectroscopic quantification, and biopsy sampling of the tumor and healthy tissue. For dose optimization, 0, 4.5, 15, and 25 mg durvalumab-680LT were used pre-CRT.Results
Quantifying in vivo fluorescence revealed a dose-dependent increase in the durvalumab-680LT signal in tumor tissues pre-CRT, with the highest fluorescence intensity and highest interpatient variability in the 25-mg group (ranges: 4.5 mg: 0.0101-0.0202 mm⁻¹, 15 mg: 0.01295-0.03225 mm⁻¹, 25 mg: 0.01720-0.0514 mm⁻¹). Sixty percent of patients (n = 3 in both dose cohorts) in the 15 mg and 25 mg cohorts exhibited high durvalumab-680LT signals with a tumor-to-healthy tissue ratio ≥2. Lower fluorescence signals were measured post-CRT compared to pre-CRT. Finally, durvalumab-680LT binding to tumor cells was confirmed using fluorescence microscopy.Conclusions
US-qFME combined with durvalumab-680LT enables the visualization of durvalumab uptake in EC and reveals interpatient variability, supporting its potential future role in selecting patients for ICI therapy.
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BibTeX
@article{waaij2026visualizing,
title = {{Visualizing the distribution of durvalumab targeting PD-L1 using quantitative fluorescence imaging in patients with esophageal cancer.}},
author = {Anne M van der Waaij and Ymke J van Ginkel and Pia Volkmer and Gursah Kats-Ugurlu and Henrik K Huizinga and Sara Hone Lopez and Jacco J de Haan and Rina Bijlsma and Laurens A van der Waaij and Christina T Muijs and Anne G H Niezink and Boudewijn van Etten and Jessie Westerhof and Massimiliano di Pietro and Dominic J Robinson and Marjolijn N Lub-de Hooge and Wouter B Nagengast},
journal = {Theranostics},
year = {2026},
month = sep,
doi = {10.7150/thno.136523},
url = {https://europepmc.org/article/MED/42909237},
note = {CC BY},
}
RIS
TY - JOUR
TI - Visualizing the distribution of durvalumab targeting PD-L1 using quantitative fluorescence imaging in patients with esophageal cancer.
AU - Anne M van der Waaij
AU - Ymke J van Ginkel
AU - Pia Volkmer
AU - Gursah Kats-Ugurlu
AU - Henrik K Huizinga
AU - Sara Hone Lopez
AU - Jacco J de Haan
AU - Rina Bijlsma
AU - Laurens A van der Waaij
AU - Christina T Muijs
AU - Anne G H Niezink
AU - Boudewijn van Etten
AU - Jessie Westerhof
AU - Massimiliano di Pietro
AU - Dominic J Robinson
AU - Marjolijn N Lub-de Hooge
AU - Wouter B Nagengast
PY - 2026
DA - 2026/09/02
JO - Theranostics
DO - 10.7150/thno.136523
UR - https://europepmc.org/article/MED/42909237
AB - Rationale Immune checkpoint inhibition (ICI) targeting programmed death-1 or its ligand (PD-1/PD-L1) is being explored as an addition to standard treatment for esophageal cancer (EC) to improve response rates, yet robust methods for patient selection are lacking. The predictive value of PD-L1 expression in biopsies is inconsistent due to intra- and intertumoral heterogeneity, and the impact of neoadjuvant chemoradiotherapy (CRT) on ICI response is unclear. Improving patient selection for receiving ICI therapies in patients with EC requires a better understanding of the drug's distribution and target binding. Here, we investigated the distribution of fluorescently labelled durvalumab (durvalumab-680LT) using ultrasound-guided quantitative fluorescence molecular endoscopy (US-qFME) before and after CRT in 20 patients with EC.Methods US-qFME included in vivo mucosal fluorescence imaging, spectroscopic quantification, and biopsy sampling of the tumor and healthy tissue. For dose optimization, 0, 4.5, 15, and 25 mg durvalumab-680LT were used pre-CRT.Results Quantifying in vivo fluorescence revealed a dose-dependent increase in the durvalumab-680LT signal in tumor tissues pre-CRT, with the highest fluorescence intensity and highest interpatient variability in the 25-mg group (ranges: 4.5 mg: 0.0101-0.0202 mm⁻¹, 15 mg: 0.01295-0.03225 mm⁻¹, 25 mg: 0.01720-0.0514 mm⁻¹). Sixty percent of patients (n = 3 in both dose cohorts) in the 15 mg and 25 mg cohorts exhibited high durvalumab-680LT signals with a tumor-to-healthy tissue ratio ≥2. Lower fluorescence signals were measured post-CRT compared to pre-CRT. Finally, durvalumab-680LT binding to tumor cells was confirmed using fluorescence microscopy.Conclusions US-qFME combined with durvalumab-680LT enables the visualization of durvalumab uptake in EC and reveals interpatient variability, supporting its potential future role in selecting patients for ICI therapy.
SN - 1838-7640
ER -