caa a22 4500 445334738 CHVBK 20180317142750.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1245/s10434-011-1664-9 doi (NATIONALLICENCE)springer-10.1245/s10434-011-1664-9 Enhancing Surgical Vision by Using Real-Time Imaging of αvβ3-Integrin Targeted Near-Infrared Fluorescent Agent [Elektronische Daten] [George Themelis, Niels Harlaar, Wendy Kelder, Joost Bart, Athanasios Sarantopoulos, Gooitzen van Dam, Vasilis Ntziachristos] Background: This study was designed to improve the surgical procedure and outcome of cancer surgery by means of real-time molecular imaging feedback of tumor spread and margin delineation using targeted near-infrared fluorescent probes with specificity to tumor biomarkers. Surgical excision of cancer often is confronted with difficulties in the identification of cancer spread and the accurate delineation of tumor margins. Currently, the assessment of tumor borders is afforded by postoperative pathology or, less reliably, intraoperative frozen sectioning. Fluorescence imaging is a natural modality for intraoperative use by directly relating to the surgeon's vision and offers highly attractive characteristics, such as high-resolution, sensitivity, and portability. Via the use of targeted probes it also becomes highly tumor-specific and can lead to significant improvements in surgical procedures and outcome. Methods: Mice bearing xenograft human tumors were injected with αvβ3-integrin receptor-targeted fluorescent probe and invivo visualized by using a novel, real-time, multispectral fluorescence imaging system. Confirmatory exvivo imaging, bioluminescence imaging, and histopathology were used to validate the invivo findings. Results: Fluorescence images were all in good correspondence with the confirming bioluminescence images in respect to signal colocalization. Fluorescence imaging detected all tumors and successfully guided total tumor excision by effectively detecting small tumor residuals, which occasionally were missed by the surgeon. Tumor tissue exhibited target-to-background ratio of ~4.0, which was significantly higher compared with white-light images representing the visual contrast. Histopathology confirmed the capability of the method to identify tumor negative margins with high specificity and better prediction rate compared with visual inspection. Conclusions: Real-time multispectral fluorescence imaging using tumor specific molecular probes is a promising modality for tumor excision by offering real time feedback to the surgeon in the operating room. Society of Surgical Oncology, 2011 Themelis George Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, Neuherberg, Germany aut Harlaar Niels Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, Neuherberg, Germany aut Kelder Wendy Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands aut Bart Joost Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands aut Sarantopoulos Athanasios Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, Neuherberg, Germany aut van Dam Gooitzen Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands aut Ntziachristos Vasilis Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, Neuherberg, Germany aut Annals of Surgical Oncology Springer-Verlag 18/12(2011-11-01), 3506-3513 1068-9265 18:12<3506 2011 18 10434 https://doi.org/10.1245/s10434-011-1664-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-011-1664-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Themelis George Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, Neuherberg, Germany aut NATIONALLICENCE 700 1- Harlaar Niels Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, Neuherberg, Germany aut NATIONALLICENCE 700 1- Kelder Wendy Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Bart Joost Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Sarantopoulos Athanasios Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, Neuherberg, Germany aut NATIONALLICENCE 700 1- van Dam Gooitzen Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Ntziachristos Vasilis Institute for Biological and Medical Imaging (IBMI), Technische Universität München and Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, Neuherberg, Germany aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/12(2011-11-01), 3506-3513 1068-9265 18:12<3506 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer