Abstract
ObjectiveTo evaluate the imaging potential of a novel near-infrared (NIR) probe conjugated to COC183B2 monoclonal antibodies (MAb) in ovarian cancer (OC).MethodsThe expression of OC183B2 antigen in OC was determined by immunohistochemical (IHC) staining using tissue microarrays with the H-score system and immunofluorescence (IF) staining of tumor cell lines. Imaging probes with the NIR fluorescent dye cyanine 7 (Cy7) conjugated to COC183B2 Mab were chemically engineered. OC183B2-positive human OC cells (SKOV3-Luc) were injected subcutaneously into BALB/c nude mice. Bioluminescent imaging (BLI) was performed to detect tumor location and growth. COC183B2-Cy7 at 1.1, 3.3, 10, or 30 μg were used for in vivo fluorescence imaging, and phosphate-buffered saline (PBS), free Cy7 dye and mouse isotype immunoglobulin G (IgG)-Cy7 (delivered at the same doses as COC183B2-Cy7) were used as controls. ResultsThe expression of OC183B2 with a high H-score was more prevalent in OC tissue than fallopian tube (FT) tissue. Among 417 OC patients, the expression of OC183B2 was significantly correlated with the histological subtype, histological grade, residual tumor size, relapse state and survival status. IF staining demonstrated that COC183B2 specifically expressed in SKOV3 cells but not HeLa cells. In vivo NIR fluorescence imaging indicated that COC183B2-Cy7 was mainly distributed in the xenograft and liver with optimal tumor-to-background (T/B) ratios in the xenograft at 30 μg dose. The highest fluorescent signals in the tumor were observed at 96 h post-injection (hpi). Ex vivo fluorescence imaging revealed the fluorescent signals mainly from the tumor and liver. IHC analysis confirmed that xenografts were OC183B2 positive. ConclusionsCOC183B2 is a good candidate for NIR fluorescence imaging and imaging-guided surgery in OC.
Highlights
Ovarian cancer (OC) is the most lethal gynecologic malignancy
This study evaluated the specificity of COC183B2 antibody in OC using immunohistochemical (IHC) and immunofluorescence (IF) staining and investigated the feasibility of using COC183B2-cyanine 7 (Cy7) as an in vivo NIR fluorescent imaging probe
Concentrated COC183B2 antibody was prepared from qualified mouse ascites, and antigen-binding specificity of COC183B2 antibody was detected by enzyme-linked immunosorbent assay (ELISA) using OCassociated antigen OC183B2 (Figure 1B)
Summary
Ovarian cancer (OC) is the most lethal gynecologic malignancy. There are an estimated 14,070 OC-related deaths in the United States in 2018, making OC the fifth leading cause of mortality among female cancer patients [1]. The understanding and treatments for OC have developed rapidly in recent decades, the prognosis of advanced-stage www.cjcrcn.org. OC patients, especially epithelial tumors, remains far from satisfactory. Cytoreductive surgery combined with chemotherapy is the current mainstream OC treatment. The degree of cytoreduction is one of the most important prognostic factors. Since surgeons still rely primarily on inaccurate direct visualization methods and empirical tactile feedback to determine tumor margins, optimal cytoreductive surgery results are not achievable, which are defined as minimal residual lesions smaller than 1 cm
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