Preclinical Evaluation of a Fluorescent Probe Targeting Receptor CDCP1 for Identification of Ovarian Cancer

• Published in: Molecular pharmaceutics Vol. 18; no. 9; pp. 3464 - 3474
• Main Authors: He, Yaowu, Khan, Tashbib, Kryza, Thomas, Jones, Martina L, Goh, Justin B, Lyons, Nicholas J, Pearce, Lesley A, Lee, Michael D, Gough, Madeline, Rogers, Rebecca, Davies, Claire M, Gilks, C. Blake, Hodgkinson, Thomas, Lourie, Rohan, Barry, Sinead C, Perrin, Lewis C, Williams, Charlotte C, Puttick, Simon, Adams, Timothy E, Munro, Trent P, Hooper, John D, Chetty, Naven
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 06.09.2021
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - chemistry; Antigens, Neoplasm; Cell Adhesion Molecules - antagonists & inhibitors; Cell Line, Tumor; Female; Fluorescent Dyes - administration & dosage; Fluorescent Dyes - chemistry; Humans; Indocyanine Green - administration & dosage; Indocyanine Green - chemistry; Injections, Intravenous; Mice; Optical Imaging - methods; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - pathology; Xenograft Model Antitumor Assays; endoscopy; CDCP1; intraoperative imaging; ovarian cancer; indocyanine green
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.1c00401

Optimal cytoreduction for ovarian cancer is often challenging because of aggressive tumor biology and advanced stage. It is a critical issue since the extent of residual disease after surgery is the key predictor of ovarian cancer patient survival. For a limited number of cancers, fluorescence-guided surgery has emerged as an effective aid for tumor delineation and effective cytoreduction. The intravenously administered fluorescent agent, most commonly indocyanine green (ICG), accumulates preferentially in tumors, which are visualized under a fluorescent light source to aid surgery. Insufficient tumor specificity has limited the broad application of these agents in surgical oncology including for ovarian cancer. In this study, we developed a novel tumor-selective fluorescent agent by chemically linking ICG to mouse monoclonal antibody 10D7 that specifically recognizes an ovarian cancer-enriched cell surface receptor, CUB-domain-containing protein 1 (CDCP1). 10D7ICG has high affinity for purified recombinant CDCP1 and CDCP1 that is located on the surface of ovarian cancer cells in vitro and in vivo. Our results show that intravenously administered 10D7ICG accumulates preferentially in ovarian cancer, permitting visualization of xenograft tumors in mice. The data suggest CDCP1 as a rational target for tumor-specific fluorescence-guided surgery for ovarian cancer.