Print Email Facebook Twitter uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery Title uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery Author Boonstra, M.C. Van Driel, P.B.A.A. Van Willigen, D.M. Stammes, M.A. Prevoo, H.A.J.M. Tummers, Q.R.J.G. Mazar, A.P. Beekman, F.J. Kuppen, P.J.K. Van de Velde, C.J.H. Löwik, C.W.G.M. Frangioni, J.V. Van Leeuwen, F.W.B. Sier, C.F.M. Vahrmeijer, A.L. Faculty Applied Sciences Department RST/Radiation, Science and Technology Date 2015-03-29 Abstract Pre- and intraoperative diagnostic techniques facilitating tumor staging are of paramount importance in colorectal cancer surgery. The urokinase receptor (uPAR) plays an important role in the development of cancer, tumor invasion, angiogenesis, and metastasis and over-expression is found in the majority of carcinomas. This study aims to develop the first clinically relevant anti-uPAR antibody-based imaging agent that combines nuclear (111In) and real-time near-infrared (NIR) fluorescent imaging (ZW800-1). Conjugation and binding capacities were investigated and validated in vitro using spectrophotometry and cell-based assays. In vivo, three human colorectal xenograft models were used including an orthotopic peritoneal carcinomatosis model to image small tumors. Nuclear and NIR fluorescent signals showed clear tumor delineation between 24h and 72h post-injection, with highest tumor-to-background ratios of 5.0 ± 1.3 at 72h using fluorescence and 4.2 ± 0.1 at 24h with radioactivity. 1-2 mm sized tumors could be clearly recognized by their fluorescent rim. This study showed the feasibility of an uPAR-recognizing multimodal agent to visualize tumors during image-guided resections using NIR fluorescence, whereas its nuclear component assisted in the pre-operative non-invasive recognition of tumors using SPECT imaging. This strategy can assist in surgical planning and subsequent precision surgery to reduce the number of incomplete resections. Subject image-guided surgerynear-infraredSPECTdual labelingcolorectal To reference this document use: http://resolver.tudelft.nl/uuid:cb7bfa4b-0e1c-46b0-a670-240514af4868 Publisher Impact Journals ISSN 1949-2553 Source Oncotarget, 2015 Part of collection Institutional Repository Document type journal article Rights (c) 2015 The Author(s)This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Files PDF Beekman_2015.pdf 1.25 MB Close viewer /islandora/object/uuid:cb7bfa4b-0e1c-46b0-a670-240514af4868/datastream/OBJ/view