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.