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Fluorescence-guided surgery (FGS) aids in intraoperative identification of tumor-positive resection margins. This study aims to assess the feasibility of urokinase plasminogen activator receptor (uPAR) targeting antibody fragments for FGS in a direct comparison with their parent IgG in various relevant in vivo models.<\/jats:p>\n            <\/jats:sec><jats:sec>\n              <jats:title>Procedures<\/jats:title>\n              <jats:p>Humanized anti-uPAR monoclonal antibody MNPR-101 (uIgG) was proteolytically digested into F(ab\u2019)2 and Fab fragments named uFab2 and uFab. Surface plasmon resonance (SPR) and cell assays were used to determine <jats:italic>in vitro<\/jats:italic> binding before and after fluorescent labeling with IRDye800CW. Mice bearing subcutaneous HT-29 human colonic cancer cells were imaged serially for up to 120\u00a0h after fluorescent tracer administration. Imaging characteristics and ex vivo organ biodistribution were further compared in orthotopic pancreatic ductal adenocarcinoma (BxPc-3-luc2), head-and-neck squamous cell carcinoma (OSC-19-luc2-GFP), and peritoneal carcinomatosis (HT29-luc2) models using the clinical Artemis fluorescence imaging system.<\/jats:p>\n            <\/jats:sec><jats:sec>\n              <jats:title>Results<\/jats:title>\n              <jats:p>Unconjugated and conjugated uIgG, uFab2, and uFab specifically recognized uPAR in the nanomolar range as determined by SPR and cell assays. Subcutaneous tumors were clearly identifiable with tumor-to-background ratios (TBRs)\u2009&gt;\u20092 after 72\u00a0h for uIgG-800F and 24\u00a0h for uFab2-800F and uFab-800F. For the latter two, mean fluorescence intensities (MFIs) dipped below predetermined threshold after 72\u00a0h and 36\u00a0h, respectively. Tumors were easily identified in the orthotopic models with uIgG-800F consistently having the highest MFIs and uFab2-800F and uFab-800F having similar values. In biodistribution studies, kidney and liver fluorescence approached tumor fluorescence after uIgG-800F administration and surpassed tumor fluorescence after uFab2-800F or uFab-800F administration, resulting in interference in the abdominal orthotopic mouse models.<\/jats:p>\n            <\/jats:sec><jats:sec>\n              <jats:title>Conclusions<\/jats:title>\n              <jats:p>In a side-by-side comparison, FGS with uPAR-targeting antibody fragments compared with the parent IgG resulted in earlier tumor visualization at the expense of peak fluorescence intensity.<\/jats:p>\n            <\/jats:sec>","DOI":"10.1007\/s11307-021-01657-2","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T05:45:01Z","timestamp":1634103901000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Side-by-Side Comparison of uPAR-Targeting Optical Imaging Antibodies and Antibody Fragments for Fluorescence-Guided Surgery of Solid Tumors"],"prefix":"10.1007","author":[{"given":"Victor M.","family":"Baart","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Labrinus","family":"van Manen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shadhvi S.","family":"Bhairosingh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floris A.","family":"Vuijk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Iamele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo","family":"de Jonge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Scotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Resnati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Cordfunke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J. 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Experiments were performed in accordance with the code of practice \u201cDierproeven In Het Kankeronderzoek.\u201d All applicable institutional and\/or national guidelines for the care and use of animals were followed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statement of Human and Animal Rights"}},{"value":"Dr. Iamele, Dr. de Jonge, and Dr Scotti report non-financial support from Ardis S.r.l., during the conduct of the study. Dr. Mazar reports personal fees and other from Monopar Therapeutics, outside the submitted work. In addition, Dr. Mazar has a patent US 8105602; US 8101726 issued. All other authors have nothing to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}