CD24 靶向的术中荧光图像引导手术导致临床前原位手术模型中卵巢癌的细胞减灭术得到改善。
CD24-targeted intraoperative fluorescence image-guided surgery leads to improved cytoreduction of ovarian cancer in a preclinical orthotopic surgical model.
机构信息
Center for Cancer Biomarkers, CCBIO, Department of Clinical Science, University of Bergen, Jonas Lies vei 91B, 5021 Bergen, Norway.
Center for Cancer Biomarkers, CCBIO, Department of Clinical Science, University of Bergen, Jonas Lies vei 91B, 5021 Bergen, Norway; Department of Radiology, Erasmus Medical Centre, 3000 CA Rotterdam, the Netherlands.
出版信息
EBioMedicine. 2020 Jun;56:102783. doi: 10.1016/j.ebiom.2020.102783. Epub 2020 May 23.
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].
背景
在卵巢癌患者中，完整切除是一个关键的预后指标，肿瘤靶向荧光图像引导手术（FIGS）的应用导致在细胞减灭术中腹膜转移的检测得到改善。CD24 在卵巢癌中高度表达，已被证明是肿瘤靶向成像的合适生物标志物。
方法
在高分级浆液性卵巢癌（HGSOC）的细胞系和异质患者来源的异种移植（PDX）肿瘤样本中研究了 CD24 的表达。在将单克隆抗体 CD24 与近红外染料 Alexa Fluor 750 缀合并评估最佳药理参数（OV-90，n=21）后，对原位 HGSOC 转移性异种移植（OV-90，n=16）进行了细胞减灭术，并实时反馈。比较了术中 CD24 靶向荧光引导与单纯白光和触诊的影响，并在术后监测疾病的复发（OV-90，n=12）。进一步在四个临床注释的转移性 HGSOC 原位 PDX 模型中评估了 CD24-AF750，以验证术中引导的转化潜力。
结果
与标准白光手术相比，CD24 靶向术中近红外 FIGS 显著（47•3%）提高了肿瘤的检测和切除率，并降低了术后肿瘤负荷在原位 HGSOC 异种移植中。CD24-AF750 允许在四个 HGSOC PDX 中识别肉眼不可见的微小肿瘤病变。
解释
CD24 靶向 FIGS 具有转化潜力，可作为改善卵巢癌减瘤手术的辅助手段。
资助
本研究得到了 H2020 计划 MSCA-ITN [675743]、Helse Vest RHF 和 Helse Bergen HF [911809、911852、912171、240222、911974、HV1269]、挪威癌症协会 [182735] 以及挪威研究理事会卓越中心资助计划 [223250、262652] 的支持。
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