一种新型卵巢癌特异性荧光抗体探针用于靶向近红外荧光成像的评估。
Evaluation of a novel ovarian cancer-specific fluorescent antibody probe for targeted near-infrared fluorescence imaging.
机构信息
Department of Obstetrics and Gynecology, Peking University People's Hospital, No. 11, Xi-Zhi-Men South Street, Xi Cheng District, Beijing, 100044, China.
Center of Gynecologic Oncology, Peking University People's Hospital, No. 11, Xi-Zhi-Men South Street, Xi Cheng District, Beijing, 100044, China.
出版信息
World J Surg Oncol. 2020 Apr 6;18(1):66. doi: 10.1186/s12957-020-01843-6.
BACKGROUND
To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance.
METHODS
The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96 h postinjection, and the biodistribution assays were performed using NIRF imaging.
RESULTS
In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs.
CONCLUSIONS
COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.
背景
为满足临床需求，荧光引导手术作为一种新技术应运而生，该技术可在手术过程中通过突出肿瘤病变来引导外科医生切除癌组织。我们旨在评估新型卵巢癌特异性抗体荧光探针 COC183B2-800（与 IRDye800CW 偶联的 COC183B2）在肿瘤特异性成像中的应用，以确定它是否有助于外科医生在荧光引导下切除恶性病变。
方法
使用免疫组织化学（IHC）检测上皮性卵巢癌（EOC）组织和细胞系中 OC183B2 抗原的表达。使用 Western blot 验证 SKOV3-Luc 肿瘤中 OC183B2 的表达。将 OC183B2 抗体和小鼠免疫球蛋白 G1（IgG1）与 IRDye800CW 偶联，开发抗体荧光探针 COC183B2-800 和 IgG-800（与 IRDye800CW 偶联的 IgG1）。构建 SKOV3-Luc 细胞的皮下小鼠肿瘤模型。进行生物发光成像（BLI）以检测肿瘤位置。注射成像剂后进行近红外荧光（NIRF）成像。注射后 96 小时处死小鼠，并进行 NIRF 成像进行生物分布测定。
结果
在 69 名 EOC 患者中，EOC 组织中 OC183B2 的总阳性率为 89.9%（62/69）。OC183B2 抗原在 SKOV3-Luc、3AO、ES2 和 A2780 细胞中表达为阳性。OC183B2 抗原可在 SKOV3-Luc 肿瘤中检测到。不同剂量 COC183B2-800 探针的 NIRF 成像显示肿瘤部位的荧光信号很高，与生物发光成像检测到的部位一致。COC183B2-800 组的肿瘤背景比（TBR）明显高于 IgG-800、IRDye800CW 和 PBS 组。荧光探针 COC183B2-800 主要通过肝脏代谢，不会在其他器官中积累。
结论
COC183B2-800 对 EOC 具有有效的肿瘤特异性靶向作用，是一种有前途的荧光引导手术诊断和治疗工具。
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