dc.contributor.author | Kleinmanns, Katrin | |
dc.contributor.author | Fosse, Vibeke Samuelsen | |
dc.contributor.author | Davidson, Ben | |
dc.contributor.author | de Jalón, Elvira Garcia | |
dc.contributor.author | Tenstad, Olav | |
dc.contributor.author | Bjørge, Line | |
dc.contributor.author | McCormack, Emmet | |
dc.date.accessioned | 2021-03-25T07:50:38Z | |
dc.date.available | 2021-03-25T07:50:38Z | |
dc.date.created | 2020-06-09T14:49:47Z | |
dc.date.issued | 2020 | |
dc.Published | EBioMedicine. 2020, 56:102783 1-12. | |
dc.identifier.issn | 2352-3964 | |
dc.identifier.uri | https://hdl.handle.net/11250/2735390 | |
dc.description.abstract | Background
The completeness of resection is a key prognostic indicator in patients with ovarian cancer, and the application of tumour-targeted fluorescence image-guided surgery (FIGS) has led to improved detection of peritoneal metastases during cytoreductive surgery. CD24 is highly expressed in ovarian cancer and has been shown to be a suitable biomarker for tumour-targeted imaging.
Methods
CD24 expression was investigated in cell lines and heterogenous patient-derived xenograft (PDX) tumour samples of high-grade serous ovarian carcinoma (HGSOC). After conjugation of the monoclonal antibody CD24 to the NIR dye Alexa Fluor 750 and the evaluation of the optimal pharmacological parameters (OV-90, n = 21), orthotopic HGSOC metastatic xenografts (OV-90, n = 16) underwent cytoreductive surgery with real-time feedback. The impact of intraoperative CD24-targeted fluorescence guidance was compared to white light and palpation alone, and the recurrence of disease was monitored post-operatively (OV-90, n = 12). CD24-AF750 was further evaluated in four clinically annotated orthotopic PDX models of metastatic HGSOC, to validate the translational potential for intraoperative guidance.
Findings
CD24-targeted intraoperative NIR FIGS significantly (47•3%) improved tumour detection and resection, and reduced the post-operative tumour burden compared to standard white-light surgery in orthotopic HGSOC xenografts. CD24-AF750 allowed identification of minuscule tumour lesions which were undetectable with the naked eye in four HGSOC PDX.
Interpretation
CD24-targeted FIGS has translational potential as an aid to improve debulking surgery of ovarian cancer.
Funding
This study was supported by the H2020 program MSCA-ITN [675743], Helse Vest RHF, and Helse Bergen HF [911809, 911852, 912171, 240222, 911974, HV1269], as well as by The Norwegian Cancer Society [182735], and The Research Council of Norway through its Centres of excellence funding scheme [223250, 262652]. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/deed.no | * |
dc.title | CD24-targeted intraoperative fluorescence image-guided surgery leads to improved cytoreduction of ovarian cancer in a preclinical orthotopic surgical model | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2020 The Authors. | en_US |
dc.source.articlenumber | 102783 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | https://doi.org/10.1016/j.ebiom.2020.102783 | |
dc.identifier.cristin | 1814594 | |
dc.source.journal | EBioMedicine | en_US |
dc.source.40 | 56:102783 | |
dc.relation.project | Norges forskningsråd: 223250 | en_US |
dc.relation.project | Norges forskningsråd: 262652 | en_US |
dc.identifier.citation | EBioMedicine. 2020, 56, 102783. | en_US |
dc.source.volume | 56 | en_US |