Improved Ex Vivo Fluorescence Imaging of Human Head and Neck Cancer Using the Peptide Tracer TPP-IRDye800 Targeting Membrane-bound Hsp70 on Tumor Cells

Overview

Journal Br J Cancer

Specialty Oncology

Date 2024 Oct 15

PMID 39406917

Authors

Katharina L K Holzmann

Johanna L Wolf

Stefan Stangl

Philipp Lennartz

Atsuko Kasajima

Carolin Mogler

Bernhard Haller

Eva-Vanessa Ebert

Daniel Jira

Maren L A Lauterbach

Franziska von Meyer

Leonhard Stark

Leonie Mauch

Benedikt Schmidl

Barbara Wollenberg

Gabriele Multhoff

Markus Wirth

Affiliations

Soon will be listed here.

Abstract

Background: The primary goal of surgery in HNSCC is the complete resection of tumor cells with maximum preservation of normal tissue. The membrane Hsp70-targeting fluorescence labelled peptide TPP-IRDye800 represents a promising tool for real-time intraoperative tumor visualization, enabling the detection of true tumor margins, critical isles of high-grade dysplasia and LN metastases.

Methods: Membrane Hsp70 (mHsp70) expression on HNSCC cell lines and primary HNSCC was determined by flow cytometry and fluorescence microscopy using FITC-conjugated mAb cmHsp70.1 and TPP. TPP-IRDye800 was sprayed on freshly resected tumor material of immunohistochemically confirmed HNSCC and LN metastases for tumor imaging. TBRs were compared using TPP-IRDye800 and Cetuximab-IRDye680, recognizing EGFR.

Results: mHsp70 expressing HNSCC cells specifically bind and internalize TPP in vitro. The TBR (2.56 ± 0.39) and AUC [0.98 CI, 0.95-1.00 vs. 0.91 CI, 0.85-0.97] of TPP-IRDye800 on primary HNSCC was significantly higher than Cetuximab-IRDye680 (1.61 ± 0.39) (p = 0.0068) and TPP-IRDye800 provided a superior tumor delineation. Fluorescence imaging showed higher AUC values than a visual inspection by surgeons [0.97 CI, 0.94-1.00 vs. 0.92 CI, 0.88-0.97] (p = 0.048). LN metastases could be visualized using TPP-IRDye800. Real-time tissue delineation was confirmed using the clinically applied KARL-STORZ imaging system.

Conclusion: TPP-IRDye800 is a promising fluorescence imaging probe for HNSCC.

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