Laboratory for In vivo Cellular and Molecular Imaging, ICMI-BEFY, Vrije Universiteit Brussel, Laabeeklaan 103, 1090, Jette, Brussels, Belgium.
Department of Oncological Surgery, UZ Brussel, Brussels, Belgium.
Mol Imaging Biol. 2018 Jun;20(3):361-367. doi: 10.1007/s11307-017-1134-2.
Debulking followed by combination chemotherapy is currently regarded as the most effective treatment for advanced ovarian cancer. Prognosis depends drastically on the degree of debulking. Accordingly, near-infrared (NIR) fluorescence imaging has been proposed to revolutionize cancer surgery by acting as a sensitive, specific, and real-time tool enabling visualization of cancer lesions. We have previously developed a NIR-labeled nanobody that allows fast, specific, and high-contrast imaging of HER2-positive tumors. In this study, we applied this tracer during fluorescence-guided surgery in a mouse model and investigated the effect on surgical efficiency.
0.5 × 10 SKOV3.IP1-Luc+ cells were inoculated intraperitoneally in athymic mice and were allowed to grow for 30 days. Two nanomoles of IRDye800CW-anti-HER2 nanobody was injected intravenously. After 1h30, mice were killed, randomized in two groups, and subjected to surgery. In the first animal group (n = 7), lesions were removed by a conventional surgical protocol, followed by excision of remaining fluorescent tissue using a NIR camera. The second group of mice (n = 6) underwent directly fluorescence-guided surgery. Bioluminescence imaging was performed before and after surgery. Resected tissue was categorized as visualized during conventional surgery or not, fluorescent or not, and bioluminescent positive or negative.
Fluorescence imaging allowed clear visualization of tumor nodules within the abdomen, up to submillimeter-sized lesions. Fluorescence guidance resulted in significantly reduced residual tumor as compared to conventional surgery. Moreover, sensitivity increased from 59.3 to 99.0 %, and the percentage of false positive lesions detected decreased from 19.6 to 7.1 %.
This study demonstrates the advantage of intraoperative fluorescence imaging using nanobody-based tracers on the efficiency of debulking surgery.
减瘤术联合化疗目前被认为是治疗晚期卵巢癌最有效的方法。预后与减瘤术的程度密切相关。因此，近红外（NIR）荧光成像是通过充当一种敏感、特异和实时的工具来实现癌症病变的可视化，从而有望彻底改变癌症手术。我们之前开发了一种近红外标记的纳米抗体，可用于快速、特异和高对比度的 HER2 阳性肿瘤成像。在这项研究中，我们在小鼠模型中应用该示踪剂进行荧光引导手术，并研究了其对手术效率的影响。
将 0.5×10 SKOV3.IP1-Luc+细胞经腹腔接种于无胸腺小鼠中，培养 30 天。静脉注射 2 纳摩尔 IRDye800CW-抗 HER2 纳米抗体。1h30 后处死小鼠，随机分为两组进行手术。在第一组动物（n=7）中，通过常规手术方案切除病变，然后使用 NIR 相机切除剩余的荧光组织。第二组小鼠（n=6）直接进行荧光引导手术。手术前后进行生物发光成像。对切除的组织进行分类，分为常规手术时可见的、荧光的、生物发光阳性的或不可见的、非荧光的、生物发光阴性的。
荧光成像可清晰显示腹部内的肿瘤结节，最小可达亚毫米大小的病变。与常规手术相比，荧光引导可显著减少残留肿瘤。此外，灵敏度从 59.3%提高到 99.0%，假阳性病变的检出率从 19.6%下降到 7.1%。
本研究证明了使用纳米抗体为基础的示踪剂进行术中荧光成像在减瘤手术效率方面的优势。
