uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery.
uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery.
复制标题
DOI：
10.18632/oncotarget.3680
复制
发表时间：
2015-06-10
期刊：
影响因子：
--
通讯作者：
Vahrmeijer AL
中科院分区：
文献类型：
--
作者：
Boonstra MC;van Driel PB;van Willigen DM;Stammes MA;Prevoo HA;Tummers QR;Mazar AP;Beekman FJ;Kuppen PJ;van de Velde CJ;Löwik CW;Frangioni JV;van Leeuwen FW;Sier CF;Vahrmeijer AL
术前和术中诊断技术促进肿瘤分期在结直肠癌手术中至关重要。尿激酶受体（uPAR）在癌症的发展、肿瘤侵袭、血管生成和转移中起着重要作用，在大多数癌症中都存在过表达。本研究旨在开发首个结合核（111In）和实时近红外（NIR）荧光成像（ZW800-1）的临床相关抗upar抗体为基础的显像剂。利用分光光度法和细胞法对其偶联和结合能力进行了体外研究和验证。在体内，使用了三种人类结肠异种移植模型，包括原位腹膜癌模型来成像小肿瘤。注射后24h至72h，核和近红外荧光信号显示肿瘤清晰，荧光检测显示72h肿瘤与背景的比值最高，为5.0±1.3，放射性检测显示24h肿瘤与背景的比值最高，为4.2±0.1。1 ~ 2mm大小的肿瘤可通过荧光边缘清晰识别。这项研究表明，upar识别多模态药物在使用近红外荧光成像的图像引导切除过程中可视化肿瘤的可行性，而其核成分则有助于使用SPECT成像进行术前非侵入性肿瘤识别。该策略有助于手术计划和后续的精确手术，以减少不完全切除的数量。
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.