Evaluation of a novel ovarian cancer-specific fluorescent antibody probe for targeted near-infrared fluorescence imaging

Abstract

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.

Near‐infrared dye‐labeled antibody COC183B2 enables detection of tiny metastatic ovarian cancer and optimizes fluorescence‐guided surgery

“…The COC183B2 monoclonal antibody was developed in our laboratory with independent intellectual property rights. Previously, we found that positive OC183B2 expression in 89.9% of EOC patients 13 . OC183B2 expression could be detected in the four main histologic types of EOC, serous, mucinous, clear cell, and endometrioid EOC, as well as in early‐stage and low‐grade EOC 13 .…”

“…13 OC183B2 expression could be detected in the four main histologic types of EOC, serous, mucinous, clear cell, and endometrioid EOC, as well as in early-stage and low-grade EOC. 13 However, a previous report showed negative FR expression in mucinous EOC. 25 Clear cell and mucinous EOC tend to go undiagnosed, and they cannot be detected by PET/CT.…”

“…COC183B2, which was generated in our laboratory using hybridoma technology, is an immunoglobulin G1 (IgG1) subtype antibody with independent intellectual property rights. COC183B2 targets the ovarian cancer‐associated antigen OC183B2, which is expressed in 89.9% of epithelial ovarian cancer (EOC) tissues 11‐13 but rarely expressed in normal tissues 14 . Previously, we conjugated COC183B2 with 131 I, and the results showed that 131 I‐COC183B2 can localize EOC by radioimmunoimaging in affected patients 14 .…”

Updates on fluorescent probes and open‐field imaging methods for fluorescence‐guided cytoreductive surgery for epithelial ovarian cancer: A review

“…Chen et al demonstrated OC183B2 expression (61.2%-89.9%) in OC. 49,50 They subsequently developed COC183B2-Cy7 (Cy7-conjugated COC183B2) and COC183B2-800 (IRDye 800CW-conjugated COC183B2). 49,50 Interestingly, the two fluorescent probes showed relatively high fluorescence signals in the liver.…”

Surgery-Guided Removal of Ovarian Cancer Using Up-Converting Nanoparticles

“…One approach to aiding surgical tumor removal focuses on targeting fluorescent probes specifically to ovarian cancer. The most clinically advanced strategy for fluorescent detection of ovarian tumors (but not yet approved) is conjugating a fluorescent dye to folate, which binds to folate receptors that are highly expressed in ovarian cancer cells. ,, However, over-expression of this receptor varies widely between different tumors, and it is present in lymph nodes and other normal tissue, leading to false-positive signals. − Some efforts to lower false-positive signals involve using near-infrared (NIR) fluorophores. Although they produce better tumor-to-background ratios, they involve multicamera setups that must be processed in parallel in order to achieve real-time detection. − …”