Publications: Image-guided Surgery

Intraoperative Near-Infrared Fluorescence Tumor Imaging with Vascular Endothelial Growth Factor and Human Epidermal Growth Factor Receptor 2 Targeting Antibodies
Anton G.T. Terwisscha van Scheltinga 1,2 , Gooitzen M. van Dam 3 , Wouter B. Nagengast 1 , Vasilis Ntziachristos 4 , Harry Hollema 5 , Jennifer L. Herek 6 , Carolien P. Schro¨der 1 , Jos G.W. Kosterink 2 , Marjolijn N. Lub-de Hoog 2,7 , and Elisabeth G.E. de Vries 1

1 Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands; 2 Department of Hospital and Clinical Pharmacy, University Medical Center Groningen, Groningen, The Netherlands; 3 Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands; 4 Institute for Biological and Medical Imaging, Technical University of Munich and Helmholtz Center Munich, Munich, Germany; 5 Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands; 6 Optical Sciences Group, MESA1 Institute for Nanotechnology, University of Twente, Enschede, The Netherlands; and 7 Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

Van Scheltinga et al. labeled Bevacizumab (anti–vascular endothelial growth factor (VEGF) antibody) and Trastuzumab (anti–human epidermal growth factor receptor (HER) 2 antibody ) with IRDye 800CW. Tumor uptake of the fluorescent tracers and their 89Zr-labeled radioactive counterparts for PET was determined in human xenograft–bearing athymic mice 1 wk after tracer injection, followed by ex vivo biodistribution and pathologic examination. The excellent selective tumor uptake previously shown with PET of 89Zr-Bevacizumab and 89Zr-Trastuzumab in mice bearing human xenografts was also observed for the same antibodies labeled with the fluorescent dye. In addition, Trastuzumab dual-labeled with 111In-DTPA and IRDye 800CW showed a similar tumor-to-muscle ratio of 2.25 for fluorescence measurements and 2.66 in a SK-BR-3 luc1 model for SPECT.

Intraoperative imaging of fluorescent VEGF- or HER2-positive tumor lesions was performed in subcutaneous tumors and in intraperitoneally disseminated tumor models. Real-time intraoperative imaging detected tumor lesions at even the submillimeter level in intraperitoneally disseminated tumor models. The results were supported by immunohistochemistry and fluorescence microscopy analyses.

They concluded IRDye 800CW labeled antibodies targeting VEGF or HER2 allowed highly specific and sensitive detection of tumor lesions in vivo and support future clinical studies with NIR fluorescence–labeled tumor-specific antibodies in a wide range of clinical applications, including intraoperative image-guided surgery.

The have completed toxicity studies on the Bevacizumab-IRDye 800CW and are currently beginning a clinical trial with the agent.

Multispectral Real-time Fluorescence Imaging for Intraoperative Detection of the Sentinel Lymph Node in Gynecologic Oncology
Lucia M.A. Crane, George Themelis, K. Tim Buddingh, Niels J. Harlaar, Rick G. Pleijhuis, Athanasios Sarantopoulos, Ate G.J. van der Zee, Vasilis Ntziachristos, Gooitzen M. van Dam

Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen Helmholtz Zentrum, Technical University Munich, Department of Obstetrics and Gynaecology, University Medical Center Groningen
J. Visualized Expt. October (2010)

The aim of this video article is to demonstrate the detection of the Sentinel Lymph Node using intraoperative fluorescence imaging in patients with cervical and vulvar cancer. Fluorescence imaging is used in conjunction with the standard procedure, consisting of radiocolloid and a blue dye. In the future, intraoperative fluorescence imaging might replace the current method and is also easily transferable to other indications like breast cancer and melanoma.

Current concepts and future perspectives on surgical optical imaging in cancer
Vasilis Ntziachristos, Jung Sun Yoo and Gooitzen M. van Dam

Technische Universit¨at Munchen, Helmholtz Zentrum Munchen, Institute for Biological and Medical Imaging, Munich, Germany. University of Groningen, University Medical Center Groningen, Division of Abdominal and Surgical Oncology, Department of Surgery, BioOptical Imaging Center Groningen, Groningen, The Netherlands
J. Biomed. Opt. 15, 066024 (Dec 29, 2010); doi:10.1117/1.3523364

Evolving fluorescence enhanced surgical vision has the potential to shape the future of surgical procedures by improving the sensitivity and accuracy of tumor delineation (circumferential resection margin), locoregional involvement, and lymph node interrogation. It is therefore anticipated that the technology of dedicated intraoperative optical instrumentation and the employment of targeted agents will significantly grow in the future to allow for improved surgical outcome using optical imaging, i.e., a method with highly attractive characteristics to allow for high dissemination and wide acceptance into the operating room.

Image-guided surgery using optical imaging
Stijn Keereweer, Jeroen D.F. Kerrebijn, Alexander L. Vahrmeijer, Clemens W.G.M. Löwik

Department of Otorhinolaryngology, Head & Neck Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. Endocrinology Research Lab and Molecular Imaging, Leiden University Medical Center, Leiden, The Netherlands
J. Biomed. Opt. 15, 066024 (Dec 29, 2010); doi:10.1117/1.3523364

Assessment of the tumour-free margin during surgery is dependent on visual appearance and palpation of the tumour. Imaging techniques that could provide real-time visualisation of the tumour could be of great benefit. Optical imaging using near-infrared fluorescence light is a new imaging modality that has recently emerged in the field of image-guided cancer surgery.

Optical imaging techniques provide real-time visualization of the tumor for application to intra-operative image-guided surgery. Within this field, imaging in the near-infrared light spectrum offers two essential advantages: increased tissue penetration of light and an increased signal-to-background-ratio of contrast agents.

Image-guided surgery in head and neck cancer: Current practice and future directions of optical imaging
S Keereweer, HJ Sterenborg, JD Kerrebijn, PB Van Driel, RJ de Jong, and CW Löwik

Department of Otorhinolaryngology, Head & Neck Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. Endocrinology Research Lab and Molecular Imaging, Leiden University Medical Center, Leiden, The Netherlands
Head Neck. 2011 Jan 31. doi: 10.1002/hed.21625

A key aspect for the postoperative prognosis of patients with head and neck cancer is complete tumor resection. In current practice, the intraoperative assessment of the tumor-free margin is dependent on visual appearance and palpation of the tumor. Optical imaging has the potential of traversing the gap between radiology and surgery by providing real-time visualization of the tumor, thereby allowing for image-guided surgery.

Intraoperative Near-infrared Fluorescent Cholangiography (NIRFC) in Mouse Models of Bile Duct Injury: Reply
Jose-Luiz Figueiredo, Matthias Nahrendorf, Claudio Vinegoni, Ralph Weissleder
World J. Surg. July 2010

Fluorescent peptides highlight peripheral nerves during surgery in mice.
MA Whitney, JL Crisp, LT Nguyen, B Friedman, LA Gross, P Steinbach, RY Tsien, and QT Nguyen
Nat Biotechnol, Feb 2011;

Nerve preservation is an important goal during surgery. Accidental transection or injury leads to numbness, pain, weakness or paralysis. Nerves are usually identified by their appearance, relationship to nearby structures or detected by local electrical simulation. Whitney et al. showed the potential of this approach by clearly delineate peripheral nerves in mice with a fluorescently labeled peptide.

Review article: Imaging in the era of molecular oncology.
R Weissleder and MJ Pittet
Nature, Apr 2008; 452(7187): 580-9.

Advances in experimental and clinical imaging are likely to improve how cancer is understood at a systems level and, ultimately, should enable doctors not only to locate tumours but also to assess the activity of the biological processes within these tumours and to provide 'on the spot' treatment.