Theranostics · 2026
Visualizing the distribution of durvalumab targeting PD-L1 using quantitative fluorescence imaging in patients with esophageal cancer.
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van der Waaij Anne M, van Ginkel Ymke J, Volkmer Pia, Kats-Ugurlu Gursah, Huizinga Henrik K, Hone Lopez Sara, de Haan Jacco J, Bijlsma Rina, van der Waaij Laurens A, Muijs Christina T, Niezink Anne G H, van Etten Boudewijn, Westerhof Jessie, di Pietro Massimiliano, Robinson Dominic J, Lub-de Hooge Marjolijn N, Nagengast Wouter B
Аннотация
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.
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.