CD24-targeted intraoperative fluorescence image-guided surgery leads to improved cytoreduction of ovarian cancer in a preclinical orthotopic surgical model
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 , Helse Vest RHF, and Helse Bergen HF [911809, 911852, 912171, 240222, 911974, HV1269], as well as by The Norwegian Cancer Society , and The Research Council of Norway through its Centres of excellence funding scheme [223250, 262652].
|Keywords||Biomarker, Debulking surgery, HGSOC, Intraoperative imaging, Near-infrared fluorescence, Patient-derived xenograft|
|Persistent URL||dx.doi.org/10.1016/j.ebiom.2020.102783, hdl.handle.net/1765/127383|
Kleinmanns, K. (Katrin), Fosse, V. (Vibeke), Davidson, B, de Jalón, E.G. (Elvira García), Tenstad, O. (Olav), Bjørge, L. (Line), & McCormack, E. (Emmet). (2020). CD24-targeted intraoperative fluorescence image-guided surgery leads to improved cytoreduction of ovarian cancer in a preclinical orthotopic surgical model. EBioMedicine, 56. doi:10.1016/j.ebiom.2020.102783