title: Targeted imaging of α(v)β(3) expressing sarcoma tumor cells in vivo in pre-operative setting using near infrared: a potential tool to reduce incomplete surgical resection.
abstract: Tumor size and location along with efficacy of pre-operative imaging are limiting factors for optimal surgical excision for osteosarcoma. Our general hypothesis is that targeting αvβ3 integrin-rich osteosarcoma neoangiogenesis should provide improved delivery of diagnostic compounds and assist surgeons intra operatively using near-infrared imaging techniques. We evaluated in an orthotopic metastatic osteosarcoma in rats the potential of AngioStamp™ targeting αvβ3 integrins and detected intra operatively by near infrared (NIR) illumination (Fluobeam™) as a novel, intra operative imaging technique. To determine the potential of this association in improving tumor and metastasis detection, we compared the quality and sensitivity of tumor/metastasis margin delineation and tumor resection using intra-operative NIR imaging to the ones guided by pre-operative imaging (i.e., MRI subsequently confirmed by histopathological analysis). Chemotherapy being essential in osteosarcoma treatment, we evaluated the capacity of AngioStamp™ to specifically localize to the tumor after chemotherapy treatment. We showed a significantly lesser extent of healthy tissue resection after surgical excision when assessing tumor margin intra operatively using AngioStamp™/Fluobeam™ association compared to pre-operative MRI post-operatively confirmed by histopathological analysis (p<0.01). Importantly, intra-operative NIR illumination of lungs revealed more metastases than were detected by CT Scan or under intra-operative white light examination (p<0.01). Importantly, chemotherapy did not alter AngioStamp™ tumor specific targeting nor the sensitivity of tumor detection. Our preclinical data confirm the potential of intra-operative imaging for improved primary tumor and lung metastasis excision. Based on these promising results, we now propose to evaluate this approach as a mean to improve surgical excision while maintaining tumor control in other sarcoma or tumors overexpressing αvβ3 integrins.
authors: Department of Clinical Sciences, Centre Léon Berard, Lyon, France; Centre de Recherche en Cancerologie, UMR, INSERM, U1052-Equipe 11-CLB, Lyon, France. Electronic address: aurelie.dutour@lyon.unicancer.fr.
authors: Aurelie
authors: A
authors: Dutour
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 823, Institut Albert Bonniot, Grenoble, France; Université Joseph Fourier (UJF), Grenoble, France.
authors: Veronique
authors: V
authors: Josserand
authors: Centre de Recherche en Cancerologie, UMR, INSERM, U1052-Equipe 11-CLB, Lyon, France.
authors: Delphine
authors: D
authors: Jury
authors: Fluoptics, Grenoble, France.
authors: Stephanie
authors: S
authors: Guillermet
authors: Department of Biopathology and Cytology, Centre Léon Berard, Lyon, France.
authors: Anne Valerie
authors: AV
authors: Decouvelaere
authors: Department of Pediatric Orthopedic Surgery, HFME, Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
authors: Franck
authors: F
authors: Chotel
authors: Centre de Recherche en Cancerologie, UMR, INSERM, U1052-Equipe 11-CLB, Lyon, France.
authors: Thomas
authors: T
authors: Pointecouteau
authors: Fluoptics, Grenoble, France.
authors: Philippe
authors: P
authors: Rizo
authors: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 823, Institut Albert Bonniot, Grenoble, France; Université Joseph Fourier (UJF), Grenoble, France.
authors: Jean Luc
authors: JL
authors: Coll
authors: Department of Clinical Sciences, Centre Léon Berard, Lyon, France; Centre de Recherche en Cancerologie, UMR, INSERM, U1052-Equipe 11-CLB, Lyon, France; Department of Medical Oncology, Centre Léon Berard, Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
authors: Jean Yves
authors: JY
authors: Blay
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D007069:Ifosfamide / Q000494:pharmacology / Q000627:therapeutic use; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D011300:Preoperative Care; D017207:Rats, Sprague-Dawley; D012509:Sarcoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D019265:Spectroscopy, Near-Infrared
chemical_list: D039302:Integrin alphaVbeta3; D007069:Ifosfamide
keywords: Margin delineation; Metastases detection; NIR guided-surgery; Osteosarcoma