Near-infrared optical guided surgery of highly infiltrative fibrosarcomas in cats using an anti-αvß3 integrin molecular probe.

We investigated how near-infrared imaging could improve highly infiltrative spontaneous fibrosarcoma surgery in 12 cats in a clinical veterinary phase. We used an RGD-based nanoprobe at different doses and times before surgery and a portable clinical grade imaging system. All tumours were labelled by the tracer and had an overall tumour-to-healthy tissue ratio of 14±1 during surgery. No false negatives were found, and the percentage of tumour cells was linearly correlated with the fluorescence intensity. All cats recovered well and were submitted to long-term follow-up that is currently on-going 1year after the beginning of the study.

[1]  H. Jin,et al.  Integrins: roles in cancer development and as treatment targets , 2004, British Journal of Cancer.

[2]  G. Citro,et al.  Intraoperative versus postoperative electrochemotherapy in high grade soft tissue sarcomas: a preliminary study in a spontaneous feline model , 2006, Cancer Chemotherapy and Pharmacology.

[3]  Y. Fujibayashi,et al.  Noninvasive visualization and quantification of tumor αVβ3 integrin expression using a novel positron emission tomography probe, 64Cu-cyclam-RAFT-c(-RGDfK-)4. , 2011, Nuclear medicine and biology.

[4]  Vasilis Ntziachristos,et al.  Real-time intraoperative fluorescence imaging system using light-absorption correction. , 2009, Journal of biomedical optics.

[5]  C. Curti,et al.  Targeting αvβ3 Integrin: Design and Applications of Mono- and Multifunctional RGD-Based Peptides and Semipeptides , 2010 .

[6]  A. Miwa,et al.  Vascular integrin beta 3 and its relation to pulmonary metastasis of colorectal carcinoma. , 2001, Anticancer research.

[7]  W. Roos,et al.  Nanocolloidal albumin-IRDye 800CW: a near-infrared fluorescent tracer with optimal retention in the sentinel lymph node , 2012, European Journal of Nuclear Medicine and Molecular Imaging.

[8]  W. Morrison,et al.  Vaccine-associated feline sarcomas. , 2001, Journal of the American Veterinary Medical Association.

[9]  D A Benaron,et al.  Tissue Optics , 1997, Science.

[10]  Donald Gullberg,et al.  Integrins , 2009, Cell and Tissue Research.

[11]  Jean-Luc Coll,et al.  New multifunctional molecular conjugate vector for targeting, imaging, and therapy of tumors. , 2005, Molecular therapy : the journal of the American Society of Gene Therapy.

[12]  J. Bading,et al.  Integrin αβ3-Targeted Imaging of Lung Cancer , 2005 .

[13]  John V. Frangioni,et al.  First-in-human clinical trials of imaging devices: An example from optical imaging , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[14]  Ivo Que,et al.  Dual-Wavelength Imaging of Tumor Progression by Activatable and Targeting Near-Infrared Fluorescent Probes in a Bioluminescent Breast Cancer Model , 2012, PloS one.

[15]  A. Saven,et al.  Activated integrin αvβ3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Sancey Lucie,et al.  Clustering and Internalization of Integrin αvβ3 With a Tetrameric RGD-synthetic Peptide. , 2009, Molecular therapy : the journal of the American Society of Gene Therapy.

[17]  R. Weissleder,et al.  In vivo imaging of tumors with protease-activated near-infrared fluorescent probes , 1999, Nature Biotechnology.

[18]  A. Grichine,et al.  In Vivo Noninvasive Optical Imaging of Receptor-Mediated RGD Internalization Using Self-Quenched Cy5-Labeled RAFT-c(-RGDfK-)4 , 2007, Molecular imaging.

[19]  M. Golzio,et al.  Intraoperative fluorescence imaging of peritoneal dissemination of ovarian carcinomas. A preclinical study. , 2011, Gynecologic oncology.

[20]  Fluoreszenzgestützte Resektion bösartiger Hirntumoren – Durchbruch bei der Hirntumor-Operation , 2009 .

[21]  D. Boturyn,et al.  Noninvasive Optical Imaging of Ovarian Metastases Using Cy5-labeled RAFT-c(-RGDfK-)4 , 2006, Molecular imaging.

[22]  J. Frangioni,et al.  Image-Guided Surgery Using Invisible Near-Infrared Light: Fundamentals of Clinical Translation , 2010, Molecular imaging.

[23]  L. Ngo,et al.  The FLARE™ Intraoperative Near-Infrared Fluorescence Imaging System: A First-in-Human Clinical Trial in Breast Cancer Sentinel Lymph Node Mapping , 2009, Annals of Surgical Oncology.

[24]  G. Davis,et al.  Integrin expression in human melanoma cells with differing invasive and metastatic properties , 1992, Clinical & Experimental Metastasis.

[25]  R. Timpl,et al.  Arg‐Gly‐Asp constrained within cyclic pentapoptides Strong and selective inhibitors of cell adhesion to vitronectin and laminin fragment P1 , 1991, FEBS letters.

[26]  K. Kallenberg,et al.  Fluorescence-Guided Operation in Recurrent Glioblastoma Multiforme Treated with Bevacizumab—Fluorescence of the Noncontrast Enhancing Tumor Tissue? , 2012, Journal of Neurological Surgery—Part A.

[27]  D. Cheresh,et al.  Glioblastoma expression of vitronectin and the alpha v beta 3 integrin. Adhesion mechanism for transformed glial cells. , 1991, The Journal of clinical investigation.

[28]  W. Bonicki,et al.  Fluorescence-guided resection of primary and recurrent malignant gliomas with 5-aminolevulinic acid. Preliminary results. , 2012, Neurologia i neurochirurgia polska.

[29]  Merlijn Hutteman,et al.  The clinical use of indocyanine green as a near‐infrared fluorescent contrast agent for image‐guided oncologic surgery , 2011, Journal of surgical oncology.

[30]  David K. Stevenson,et al.  Tissue Optics , 1997, Science.

[31]  M. Kéramidas,et al.  Intraoperative near‐infrared image‐guided surgery for peritoneal carcinomatosis in a preclinical experimental model , 2010, The British journal of surgery.

[32]  P. Low,et al.  Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results , 2011, Nature Medicine.

[33]  Y. Fujibayashi,et al.  Positron emission tomography imaging of tumor angiogenesis and monitoring of antiangiogenic efficacy using the novel tetrameric peptide probe 64Cu-cyclam-RAFT-c(-RGDfK-)4 , 2012, Angiogenesis.

[34]  D. Boturyn,et al.  In vivo optical imaging of integrin αV-β3 in mice using multivalent or monovalent cRGD targeting vectors , 2007, Molecular Cancer.

[35]  Jean-Luc Coll,et al.  Template assembled cyclopeptides as multimeric system for integrin targeting and endocytosis. , 2004, Journal of the American Chemical Society.

[36]  M. Hendrix,et al.  Role of the alpha v beta 3 integrin in human melanoma cell invasion. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[37]  D. Cheresh,et al.  Integrins, angiogenesis and vascular cell survival. , 1996, Chemistry & biology.

[38]  David A. Cheresh,et al.  Integrins in cancer: biological implications and therapeutic opportunities , 2010, Nature Reviews Cancer.

[39]  J. Bading,et al.  Integrin alpha v beta 3-targeted imaging of lung cancer. , 2005, Neoplasia.