@inproceedings{01HTDN03Y4WZMP00D9GCS84V68,
  abstract     = {{Introduction

In surgical oncology, fluorescence imaging enables real-time visualization of tumor tissue amid healthy surroundings. The targeted tracer 7D12-s775z, a fluorescently labeled anti-EGFR Nanobody, has shown promising results in preclinical tumor delineation studies in murine models. To improve surgical margins, two applications were explored in this study: ex vivo margin assessment in human samples and fluorescence-guided surgery (FGS) in dogs with spontaneous cancer - a valuable complementary model between mouse and human studies.

Methods

Freshly excised specimens of head and neck carcinomas from human patients were incubated with 7D12-s775z or a block solution containing unlabeled Nanobody and imaged on a fluorescence scanner. In parallel, dogs with spontaneous cancer received 1.74 mg/m2 of 7D12-s775z intravenously 1 hour before surgery as part of a dose-escalating study. Intraoperatively, imaging of the tumor and sentinel lymph node was performed using a near-infrared fluorescent camera. After resection, the specimens were imaged ex vivo using the same camera and a flatbed fluorescence scanner. Standard histopathological processing and EGFR immunohistochemical (IHC) analysis were conducted on all samples.

Results/Discussion

A higher fluorescent signal was observed in the tumor compared to surrounding normal tissue, both ex vivo and in vivo. Quantitative analysis on all tissue slices further confirmed the higher mean fluorescence intensity in tumoral tissue compared to background. Histopathological analysis demonstrated a correlation between EGFR-expression and fluorescence, substantiating the specificity of the tracer. The topical application of the compound on six ex vivo human samples showcased its uptake by EGFR-expressing tumor cells (Figure 1), emphasizing the compound's potential for back-table margin assessment. Moreover, initial in vivo findings demonstrated the tracer's affinity for the tumor and metastatic lymph node at the lowest dose (Figure 2), but the signal observed during surgery was weak at low exposure times. Higher signal is expected in subsequent dose groups of this dose-escalating trial.

Conclusion

Preliminary findings suggest that 7D12-s775z effectively targets EGFR-positive tumors, enabling ex vivo and in vivo tumor cell visualization. Our results highlight the different potential clinical applications of the tracer, not only in FGS, but also as a promising tool for ex vivo margin assessment. Moreover, the ongoing trial's success in canine patients is an important milestone for advancing clinical translation to human head and neck cancer.

Novelty

This is the first reported use of Nanobody-based fluorescence-guided surgery in dogs with spontaneous cancer and topically on human samples.

Impact

Successful validation in canine patients will accelerate the clinical translation of the tracer in humans with head and neck cancer.

Disclosure

I or one of my co-authors have the following financial interest or relationship(s) to disclose regarding the subject matter of this presentation: Prof. Sophie Hernot is coinventor on patent PCT/EP2022/077690, related to s775z-labeled Nanobody.}},
  author       = {{Herreira do Valle, Nayra Cristina and Debacker, Jens and Creytens, David and Janssen, Simone and Stroet, Marcus and Pollenus, Sofie and Struys, Mathieu and Henrotte, Michaël and De Cock, Hilde and Huvenne, Wouter and Hernot, Sophie and De Rooster, Hilde}},
  booktitle    = {{19th European Molecular Imaging Meeting (EMIM 2024), Abstracts}},
  language     = {{eng}},
  location     = {{Porto, Portugal}},
  title        = {{Fluorescence-guided surgery using an anti-EGFR Nanobody in dogs with spontaneous carcinomas : translational prospects for head and neck cancer}},
  url          = {{https://www.eventclass.it/emim2024/scientific/online-program/session?s=PS+19#e128}},
  year         = {{2024}},
}