Evaluation of a targeted anti-αvβ3 integrin near-infrared fluorescent dye for fluorescence-guided resection of naturally occurring soft tissue sarcomas in dogs

Patricia Beer; Paula Grest; Christiane Krudewig; Chris Staudinger; Stefanie Ohlerth; Carla Rohrer Bley; Armin Jarosch; Houria Ech-Cherif; Enni Markkanen; Brian Park; Mirja Christine Nolff

doi:10.1007/s00259-024-06953-x

Evaluation of a targeted anti-α_vβ₃ integrin near-infrared fluorescent dye for fluorescence-guided resection of naturally occurring soft tissue sarcomas in dogs

Eur J Nucl Med Mol Imaging. 2024 Oct 22. doi: 10.1007/s00259-024-06953-x. Online ahead of print.

Authors

Affiliations

¹ Clinic for Small Animal Surgery, Vetsuisse Faculty, University Animal Hospital, University of Zurich, Zurich, Switzerland. pbeer@vetclinics.uzh.ch.
² Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
³ Clinic for Diagnostic Imaging, University Animal Hospital, Vetsuisse Faculty Zurich, University Zurich, Zurich, Switzerland.
⁴ Division of Radiation Oncology, University Animal Hospital, Vetsuisse Faculty Zurich, University Zurich, Zurich, Switzerland.
⁵ Department of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁶ Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
⁷ Clinic for Small Animal Surgery, Vetsuisse Faculty, University Animal Hospital, University of Zurich, Zurich, Switzerland.

PMID: 39436437
DOI: 10.1007/s00259-024-06953-x

Abstract

Purpose: Complete resection is a key prognostic factor for survival in patients with soft tissue sarcoma (STS), in humas and companion animals alike. Fluorescence-guided surgery could improve resection accuracy. As dogs are frequently affected by STS, they serve as a model to test an anti-α_vβ₃ integrin targeting near-infrared fluorescent (NIRF) dye (Angiostamp^TM800) for fluorescence-guided surgery in STS to evaluate its safety and feasibility in dogs, and if it translates into a clinically relevant benefit compared to the standard of care with regards to completeness of surgery and local recurrence. Furthermore, we aimed to correlate target expression and NIRF-signal intensity.

Methods: Twenty dogs with STS were randomly allocated to either receive Angiostamp™ (NIRF group) or physiologic saline (control group) preoperatively. The researchers were blinded for treatment, and resections were adapted based on the NIRF-signal, if needed. Margin status was histologically determined at the 1 and 3 cm margin. The tumor-to-background ratio was measured in native tissue biopsies and formalin-fixed tissue. The fluorescent area was compared to the corresponding tumor areas as confirmed by histology using the Dice coefficient. Target expression was quantified by immunohistochemistry and correlated to NIRF-signal ratios.

Results: A fluorescent signal was detected in all 10 tumors of the NIRF group, with a tumor-to-background ratio of 7.4 ± 5.8 in native biopsies and 13.5 ± 10.9 in formalin-fixed tissue. In the NIRF group, resection margins were adapted in 5/10 cases, leading to complete resection and preventing R1 in four of these cases. In the NIRF and control group 9/10 and 8/10 resections were R0, with one local recurrence in each group and one sarcoma-related death in the NIRF group. The NIRF-signal correlated with the histologically confirmed tumor area (Dice coefficient 0.75 ± 0.17). Target expression was higher in tumor compared to peritumoral tissue (p < 0.0003) and showed a moderate correlation with the NIRF-signal (r = 0.6516, p < 0.0001).

Conclusion: Fluorescence-guided surgery using Angiostamp™ can pinpoint residual disease in the tumor bed and contributes to an improved resection accuracy in canine STS.

Keywords: Comparative oncology; Dog; Second window sarcoma imaging; Soft tissue sarcoma; Targeted near-infrared fluorescent dye; Targeted near-infrared fluorescent imaging.

Abstract

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