Fluorescence-guided surgery for cancer patients: a proof of concept study on human xenografts in mice and spontaneous tumors in pets

// Eliane Mery 1, * , Muriel Golzio 2, * , Stephanie Guillermet 3 , Didier Lanore 4 , Augustin Le Naour 1 , Benoit Thibault 1 , Anne Francoise Tilkin-Mariame 1 , Elizabeth Bellard 2 , Jean Pierre Delord 1 , Denis Querleu 1 , Gwenael Ferron 1, * and Bettina Couderc 1, * 1 Institut Claudius Regaud –IUCT Oncopole, University Toulouse III, Toulouse, France 2 Institut de Pharmacologie et de Biologie Structurale, Universite de Toulouse, Toulouse, France 3 Fluoptics SAS, 7, parvis Louis Neel, CS 20050, 38040 Grenoble cedex 09, France 4 Clinique veterinaire Alliance, 8 Boulevard Godard, 33300 Bordeaux, France * These authors have contributed equally to this work Correspondence to: Bettina Couderc, email: Couderc.bettina@iuct-oncopole.fr Keywords: tumor targeting; optical imaging; fluorescence-guided surgery; integrins; spontaneous animal models Received: July 27, 2017     Accepted: October 28, 2017     Published: November 30, 2017 ABSTRACT Surgery is often the first treatment option for patients with cancer. Patient survival essentially depends on the completeness of tumor resection. This is a major challenge, particularly in cases of peritoneal carcinomatosis, where tumors are widely disseminated in the large peritoneal cavity. Any development to help surgeons visualize these residual cells would improve the completeness of the surgery. For non-disseminated tumors, imaging could be used to ensure that the tumor margins and the draining lymph nodes are free of tumor deposits. Near-infrared fluorescence imaging has been shown to be one of the most convenient imaging modalities. Our aim was to evaluate the efficacy of a near-infrared fluorescent probe targeting the αvβ3 integrins (Angiostamp™) for intraoperative detection of tumors using the Fluobeam® device. We determined whether different human tumor nodules from various origins could be detected in xenograft mouse models using both cancer cell lines and patient-derived tumor cells. We found that xenografts could be imaged by fluorescent staining irrespective of their integrin expression levels. This suggests imaging of the associated angiogenesis of the tumor and a broader potential utilization of Angiostamp™. We therefore performed a veterinary clinical trial in cats and dogs with local tumors or with spontaneous disseminated peritoneal carcinomatosis. Our results demonstrate that the probe can specifically visualize both breast and ovarian nodules, and suggest that Angiostamp™ is a powerful fluorescent contrast agent that could be used in both human and veterinary clinical trials for intraoperative detection of tumors.