Successful Fluorescence-Guided Surgery on Human Colon Cancer Patient-Derived Orthotopic Xenograft Mouse Models Using a Fluorophore-Conjugated Anti-CEA Antibody and a Portable Imaging System
Successful Fluorescence-Guided Surgery on Human Colon Cancer Patient-Derived Orthotopic Xenograft Mouse Models Using a Fluorophore-Conjugated Anti-CEA Antibody and a Portable Imaging System
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DOI：
10.1089/lap.2013.0418
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发表时间：
2014-04-01
影响因子：
1.3
通讯作者：
Hoffman, Robert M.
中科院分区：
文献类型：
--
作者：
Hiroshima, Yukihiko;Maawy, Ali;Hoffman, Robert M.
背景：荧光引导手术 (FGS) 可以实现亮光手术通常无法成功的癌症手术。 FGS 走向临床需要解决三个重要问题：(a) 正确的肿瘤标记，(b) 用于手术室的简单便携式成像系统，以及 (c) 用于开发该技术的类患者小鼠模型。本报告涉及所有这三个方面。 材料和方法：最初在手术后立即在非肥胖糖尿病（NOD）/严重联合免疫缺陷（SCID）小鼠中皮下建立患者结肠肿瘤。然后从 NOD/SCID 小鼠中收获肿瘤，并在裸鼠中原位传递，以制作患者来源的原位异种移植（PDOX）模型。原位植入八周后，在剖腹手术前 24 小时，将与 AlexaFluor(R) 488（Molecular Probes Inc.，尤金，俄勒冈州）缀合的单克隆抗癌胚抗原 (CEA) 抗体以单次静脉注射的形式递送至 PDOX 模型。采用手持式便携式荧光成像设备。结果：剖腹探查时，便携式荧光成像系统清晰可见原发肿瘤。切除标本的冰冻切片显微镜检查表明，抗 CEA 抗体选择性标记了结肠癌 PDOX 中的癌细胞。在荧光导航下将肿瘤完全切除。对切除标本的组织学评估表明，边缘不存在癌细胞，表明肿瘤切除成功。 FGS 动物在 6 个多月内保持无肿瘤状态。结论：本报告的结果表明，使用荧光团偶联的抗 CEA 抗体和便携式成像系统的 FGS 提高了 CEA 阳性结直肠癌的切除效果。这些数据为临床试验提供了基础。
Background: Fluorescence-guided surgery (FGS) can enable successful cancer surgery where bright-light surgery often cannot. There are three important issues for FGS going forward toward the clinic: (a) proper tumor labeling, (b) a simple portable imaging system for the operating room, and (c) patient-like mouse models in which to develop the technology. The present report addresses all three.Materials and Methods: Patient colon tumors were initially established subcutaneously in nonobese diabetic (NOD)/severe combined immune deficiency (SCID) mice immediately after surgery. The tumors were then harvested from NOD/SCID mice and passed orthotopically in nude mice to make patient-derived orthotopic xenograft (PDOX) models. Eight weeks after orthotopic implantation, a monoclonal anti-carcinoembryonic antigen (CEA) antibody conjugated with AlexaFluor((R)) 488 (Molecular Probes Inc., Eugene, OR) was delivered to the PDOX models as a single intravenous dose 24 hours before laparotomy. A hand-held portable fluorescence imaging device was used.Results: The primary tumor was clearly visible at laparotomy with the portable fluorescence imaging system. Frozen section microscopy of the resected specimen demonstrated that the anti-CEA antibody selectively labeled cancer cells in the colon cancer PDOX. The tumor was completely resected under fluorescence navigation. Histologic evaluation of the resected specimen demonstrated that cancer cells were not present in the margins, indicating successful tumor resection. The FGS animals remained tumor free for over 6 months.Conclusions: The results of the present report indicate that FGS using a fluorophore-conjugated anti-CEA antibody and portable imaging system improves efficacy of resection for CEA-positive colorectal cancer. These data provide the basis for clinical trials.