uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery

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 majo...

Full description

Bibliographic Details
Main Authors:	Boonstra, Martin C., van Driel, Pieter B.A.A., van Willigen, Danny M., Stammes, Marieke A., Prevoo, Hendrica A.J.M., Tummers, Quirijn R.J.G., Mazar, Andrew P., Beekman, Freek J., Kuppen, Peter J.K., van de Velde, Cornelis J.H., Löwik, Clemens W.G.M., Frangioni, John V., van Leeuwen, Fijs W.B., Sier, Cornelis F.M., Vahrmeijer, Alexander L.
Format:	Online
Language:	English
Published:	Impact Journals LLC 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546465/

id	pubmed-4546465
recordtype	oai_dc
spelling	pubmed-45464652015-08-27 uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery Boonstra, Martin C. van Driel, Pieter B.A.A. van Willigen, Danny M. Stammes, Marieke A. Prevoo, Hendrica A.J.M. Tummers, Quirijn R.J.G. Mazar, Andrew P. Beekman, Freek J. Kuppen, Peter J.K. van de Velde, Cornelis J.H. Löwik, Clemens W.G.M. Frangioni, John V. van Leeuwen, Fijs W.B. Sier, Cornelis F.M. Vahrmeijer, Alexander L. Research Paper 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. Impact Journals LLC 2015-03-29 /pmc/articles/PMC4546465/ /pubmed/25895028 Text en Copyright: © 2015 Boonstra et al. http://creativecommons.org/licenses/by/2.5/ 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Boonstra, Martin C. van Driel, Pieter B.A.A. van Willigen, Danny M. Stammes, Marieke A. Prevoo, Hendrica A.J.M. Tummers, Quirijn R.J.G. Mazar, Andrew P. Beekman, Freek J. Kuppen, Peter J.K. van de Velde, Cornelis J.H. Löwik, Clemens W.G.M. Frangioni, John V. van Leeuwen, Fijs W.B. Sier, Cornelis F.M. Vahrmeijer, Alexander L.
spellingShingle	Boonstra, Martin C. van Driel, Pieter B.A.A. van Willigen, Danny M. Stammes, Marieke A. Prevoo, Hendrica A.J.M. Tummers, Quirijn R.J.G. Mazar, Andrew P. Beekman, Freek J. Kuppen, Peter J.K. van de Velde, Cornelis J.H. Löwik, Clemens W.G.M. Frangioni, John V. van Leeuwen, Fijs W.B. Sier, Cornelis F.M. Vahrmeijer, Alexander L. uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery
author_facet	Boonstra, Martin C. van Driel, Pieter B.A.A. van Willigen, Danny M. Stammes, Marieke A. Prevoo, Hendrica A.J.M. Tummers, Quirijn R.J.G. Mazar, Andrew P. Beekman, Freek J. Kuppen, Peter J.K. van de Velde, Cornelis J.H. Löwik, Clemens W.G.M. Frangioni, John V. van Leeuwen, Fijs W.B. Sier, Cornelis F.M. Vahrmeijer, Alexander L.
author_sort	Boonstra, Martin C.
title	uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery
title_short	uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery
title_full	uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery
title_fullStr	uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery
title_full_unstemmed	uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery
title_sort	upar-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery
description	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.
publisher	Impact Journals LLC
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546465/
_version_	1613262735774056448

uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery

Similar Items