Oncotarget

Research Papers:

Preliminary safety and imaging efficacy of the near-infrared fluorescent contrast agent DA364 during fluorescence-guided surgery in dogs with spontaneous superficial tumors

Sophie Favril _, Chiara Brioschi, Katrien Vanderperren, Eline Abma, Emmelie Stock, Nausikaa Devriendt, Ingeborgh Polis, Hilde De Cock, Alessia Cordaro, Luigi Miragoli, Paolo Oliva, Giovanni Valbusa, Charline Alleaume, Isabelle Tardy, Alessandro Maiocchi, Fabio Tedoldi, Francesco Blasi and Hilde de Rooster

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Oncotarget. 2020; 11:2310-2326. https://doi.org/10.18632/oncotarget.27633

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Abstract

Sophie Favril1,2,*, Chiara Brioschi3,*, Katrien Vanderperren4, Eline Abma1,2, Emmelie Stock4, Nausikaa Devriendt1, Ingeborgh Polis1, Hilde De Cock5, Alessia Cordaro3, Luigi Miragoli3, Paolo Oliva3, Giovanni Valbusa6, Charline Alleaume7, Isabelle Tardy7, Alessandro Maiocchi3, Fabio Tedoldi3, Francesco Blasi3,* and Hilde de Rooster1,2,*

1 Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium

2 Cancer Research Institute Ghent, Ghent, Belgium

3 Bracco Imaging SpA, c/o BioIndustry Park, Colleretto Giacosa, Italy

4 Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium

5 Medvet/Algemeen Medisch Laboratorium, Antwerpen, Belgium

6 Ephoran Multi-Imaging Solutions, Colleretto Giacosa, Italy

7 Bracco Suisse S.A., Plan-les-Ouates, Switzerland

* These authors contributed equally to this work

Correspondence to:

Sophie Favril,email: Sophie.Favril@ugent.be

Keywords: fluorescence-guided surgery; fluorescent contrast agent; near-infrared fluorescence imaging; spontaneous tumors; canine

Received: January 08, 2020     Accepted: May 14, 2020     Published: June 16, 2020

ABSTRACT

Tumor-targeting contrast agents may facilitate resection of solid neoplasms during fluorescence-guided surgery. Preliminary safety and imaging efficacy of the near-infrared fluorescent probe DA364 were evaluated during surgical resection of spontaneous solid tumors in 24 dogs. Intra-operative imaging was performed in situ and on excised specimens to evaluate fluorescence intensities of tumor and adjacent tissues. After standard-of-care tumor resection, the wound bed was imaged again, and additional tissue was excised if residual fluorescence was detected.

DA364 was well tolerated after intravenous administration. The median tumor-to-background ratio in situ for mammary tumors, mast cell tumors and sarcomas was 1.8 (range 1.2–3.9), 2.2 (range 1.0–5.6), and 4.2 (range 2.0–4.3), respectively. Qualitative intra-operative tumor identification was feasible in half of the cases. Remaining fluorescence was detected in four wound beds that contained residual disease, and in11 tumor-free wound beds, confirmed by histopathology.

Overall, DA364 did not raise safety concerns and showed accumulation in different types of spontaneous tumors, showing potential to pinpoint residual disease. Larger clinical trials are necessary to select accurate dosing and imaging protocols for specific indications to evaluate the sensitivity and specificity of the agent.


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