Chen Zhang1,2, Xinyu Ling3, Yanxiu Guo1,2, Cunzhong Yuan4, Hongyan Cheng1,2, Xue Ye1,2, Ruiqiong Ma1,2, Yinli Zhang5, Yi Li1, Xiaohong Chang1,2, Beihua Kong4, Tao Liu3, Heng Cui1,2. 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.
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.
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.
Authors: Emiliano Cocco; Erik M Shapiro; Sara Gasparrini; Salvatore Lopez; Carlton L Schwab; Stefania Bellone; Ileana Bortolomai; Natalia J Sumi; Elena Bonazzoli; Roberta Nicoletti; Yang Deng; W Mark Saltzman; Caroline J Zeiss; Floriana Centritto; Jonathan D Black; Dan-Arin Silasi; Elena Ratner; Masoud Azodi; Thomas J Rutherford; Peter E Schwartz; Sergio Pecorelli; Alessandro D Santin Journal: Int J Cancer Date: 2015-08-18 Impact factor: 7.396
Authors: N J Harlaar; W Kelder; A Sarantopoulos; J Bart; G Themelis; G M van Dam; V Ntziachristos Journal: Gynecol Oncol Date: 2012-12-19 Impact factor: 5.482
Authors: Karthik M Sundaram; Yilin Zhang; Anirban K Mitra; Jean-Louis K Kouadio; Katja Gwin; Anthony A Kossiakoff; Brian B Roman; Ernst Lengyel; Joseph A Piccirilli Journal: Cancer Res Date: 2017-02-15 Impact factor: 12.701
Authors: Quirijn R J G Tummers; Charlotte E S Hoogstins; Alexander A W Peters; Cor D de Kroon; J Baptist M Z Trimbos; Cornelis J H van de Velde; John V Frangioni; Alexander L Vahrmeijer; Katja N Gaarenstroom Journal: PLoS One Date: 2015-06-25 Impact factor: 3.240
Authors: Winnie Yeo; Stephen L Chan; Frankie K F Mo; Cheuk M Chu; Joyce W Y Hui; Joanne H M Tong; Anthony W H Chan; Jane Koh; Edwin P Hui; Herbert Loong; Kirsty Lee; Leung Li; Brigette Ma; Ka F To; Simon C H Yu Journal: BMC Cancer Date: 2015-05-12 Impact factor: 4.430
Authors: Rebecca W Gao; Nutte Teraphongphom; Esther de Boer; Nynke S van den Berg; Vasu Divi; Michael J Kaplan; Nicholas J Oberhelman; Steven S Hong; Elissa Capes; A Dimitrios Colevas; Jason M Warram; Eben L Rosenthal Journal: Theranostics Date: 2018-03-28 Impact factor: 11.556