BACKGROUND AND OBJECTIVES: Near-infrared (NIR) fluorescence optical imaging is a promising technique to assess the tumor margins during cancer surgery. This technique requires targeting by specific fluorescence agents to differentiate tumor from normal surrounding tissue. We assessed the feasibility of cancer detection using NIR fluorescence agents that target either αvβ3 integrins or the enhanced permeability and retention (EPR) effect in an orthotopic mouse model of oral cancer. METHODS: Binding of the integrin-targeted agent to tumor cells was assessed in vitro. Oral cancer was induced in 6 BALB/c nu/nu mice by submucosal inoculation of human OSC19-luc cells into the tongue. Tumor growth was followed with bioluminescence imaging. A combination of agents targeting integrins or EPR effect was injected followed by fluorescence imaging in vivo and ex vivo after resection of the tongues. RESULTS: Oral cancer was clearly demarcated in vitro; in vivo; and on histological analysis with sufficient tumor-to-background ratios of the contrast agents. CONCLUSION: This study demonstrates the feasibility of optical imaging of oral squamous cell carcinoma based on targeting of αvβ3 integrins and the EPR effect. Once these NIR fluorescence agents become available for clinical testing, optical image-guided surgery could reduce residual disease after oral cancer surgery.
BACKGROUND AND OBJECTIVES: Near-infrared (NIR) fluorescence optical imaging is a promising technique to assess the tumor margins during cancer surgery. This technique requires targeting by specific fluorescence agents to differentiate tumor from normal surrounding tissue. We assessed the feasibility of cancer detection using NIR fluorescence agents that target either αvβ3 integrins or the enhanced permeability and retention (EPR) effect in an orthotopic mouse model of oral cancer. METHODS: Binding of the integrin-targeted agent to tumor cells was assessed in vitro. Oral cancer was induced in 6 BALB/c nu/nu mice by submucosal inoculation of human OSC19-luc cells into the tongue. Tumor growth was followed with bioluminescence imaging. A combination of agents targeting integrins or EPR effect was injected followed by fluorescence imaging in vivo and ex vivo after resection of the tongues. RESULTS:Oral cancer was clearly demarcated in vitro; in vivo; and on histological analysis with sufficient tumor-to-background ratios of the contrast agents. CONCLUSION: This study demonstrates the feasibility of optical imaging of oral squamous cell carcinoma based on targeting of αvβ3 integrins and the EPR effect. Once these NIR fluorescence agents become available for clinical testing, optical image-guided surgery could reduce residual disease after oral cancer surgery.
Authors: Martin C Boonstra; Berend Tolner; Boudewijn E Schaafsma; Leonora S F Boogerd; Hendrica A J M Prevoo; Guarav Bhavsar; Peter J K Kuppen; Cornelis F M Sier; Bert A Bonsing; John V Frangioni; Cornelis J H van de Velde; Kerry A Chester; Alexander L Vahrmeijer Journal: Int J Cancer Date: 2015-06-22 Impact factor: 7.396
Authors: Floris P R Verbeek; Joost R van der Vorst; Quirijn R J G Tummers; Martin C Boonstra; Karien E de Rooij; Clemens W G M Löwik; A Rob P M Valentijn; Cornelis J H van de Velde; Hak Soo Choi; John V Frangioni; Alexander L Vahrmeijer Journal: Ann Surg Oncol Date: 2014-02-11 Impact factor: 5.344
Authors: P B A A van Driel; J R van der Vorst; F P R Verbeek; S Oliveira; T J A Snoeks; S Keereweer; B Chan; M C Boonstra; J V Frangioni; P M P van Bergen en Henegouwen; A L Vahrmeijer; C W G M Lowik Journal: Int J Cancer Date: 2013-12-12 Impact factor: 7.396
Authors: Martin C Boonstra; Pieter B A A van Driel; Danny M van Willigen; Marieke A Stammes; Hendrica A J M Prevoo; Quirijn R J G Tummers; Andrew P Mazar; Freek J Beekman; Peter J K Kuppen; Cornelis J H van de Velde; Clemens W G M Löwik; John V Frangioni; Fijs W B van Leeuwen; Cornelis F M Sier; Alexander L Vahrmeijer Journal: Oncotarget Date: 2015-06-10