Evaluation of COC183B2 antibody targeting ovarian cancer by near-infrared fluorescence imaging

Chen Zhang; Xinyu Ling; Yanxiu Guo; Cunzhong Yuan; Hongyan Cheng; Xue Ye; Ruiqiong Ma; Yinli Zhang; Yi Li; Xiaohong Chang; Beihua Kong; Tao Liu; Heng Cui

doi:10.21147/j.issn.1000-9604.2019.04.11

Evaluation of COC183B2 antibody targeting ovarian cancer by near-infrared fluorescence imaging

Chin J Cancer Res. 2019 Aug;31(4):673-685. doi: 10.21147/j.issn.1000-9604.2019.04.11.

Authors

Chen Zhang^{1

2}, Xinyu Ling³, Yanxiu Guo^{1

2}, Cunzhong Yuan⁴, Hongyan Cheng^{1

2}, Xue Ye^{1

2}, Ruiqiong Ma^{1

2}, Yinli Zhang⁵, Yi Li¹, Xiaohong Chang^{1

2}, Beihua Kong⁴, Tao Liu³, Heng Cui^{1

2}

Affiliations

¹ Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.
² Center of Gynecologic Oncology, Peking University People's Hospital, Beijing 100044, China.
³ State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
⁴ Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, China.
⁵ Department of Pathology, Peking University People's Hospital, Beijing 100044, China.

PMID: 31564810
PMCID: PMC6736662
DOI: 10.21147/j.issn.1000-9604.2019.04.11

Abstract

Objective: To evaluate the imaging potential of a novel near-infrared (NIR) probe conjugated to COC183B2 monoclonal antibodies (MAb) in ovarian cancer (OC).

Methods: The 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.

Results: The 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.

Conclusions: COC183B2 is a good candidate for NIR fluorescence imaging and imaging-guided surgery in OC.

Keywords: COC183B2 antibody; near-infrared fluorescence imaging; ovarian cancer.