A molecularly targeted intraoperative near-infrared fluorescence imaging agent for high-grade serous ovarian cancer Journal Article

   


Authors: Fung, K.; Sharma, S. K.; Keinänen, O.; Long Roche, K.; Lewis, J. S.; Zeglis, B. M.
Article Title: A molecularly targeted intraoperative near-infrared fluorescence imaging agent for high-grade serous ovarian cancer
Abstract: Ovarian cancer is the fifth leading cause of cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. The foundation of its management consists of cytoreductive surgery (CRS) followed by systemic chemotherapy, with the completeness of surgical resection consistently identified as one of the most important prognostic factors for the disease. The goal of our investigation is the development of a near-infrared fluorescence (NIRF) imaging agent for the intraoperative imaging of high-grade serous ovarian cancer (HGSOC). As surgeons are currently limited to the visual and manual assessment of tumor tissue during CRS, this technology could facilitate more complete resections as well as serve important functions at other points in the surgical management of the disease. Elevated levels of cancer antigen 125 (CA125) have proven a useful biomarker of HGSOC, and the CA125-targeting antibody B43.13 has shown potential as a platform for immunoPET imaging in murine models of ovarian cancer. Herein, we report the development of a NIRF imaging agent based on B43.13: ssB43.13-IR800. We site-specifically modified the heavy chain glycans of B43.13 with the near-infrared dye IRDye 800CW using a chemoenzymatic approach developed in our laboratories. SDS-PAGE analysis confirmed the specificity of the conjugation reaction, and flow cytometry, immunostaining, and fluorescence microscopy verified the specific binding of ssB43.13-IR800 to CA125-expressing OVCAR3 human ovarian cancer cells. NIRF imaging studies demonstrated that ssB43.13-IR800 can be used to image CA125-expressing HGSOC tumors in subcutaneous, orthotopic, and patient-derived xenograft mouse models. Finally, ex vivo analyses confirmed that ssB43.13-IR800 can bind and identify CA125-expressing cells in primary tumor and metastatic lymph node samples from human patients with HGSOC.
Keywords: ovarian cancer; ca125; near-infrared fluorescence imaging; immunoconjugate; site-specific bioconjugation; b43.13; ir800cwdye
Journal Title: Molecular Pharmaceutics
Volume: 17
Issue: 8
ISSN: 1543-8384
Publisher: American Chemical Society  
Date Published: 2020-08-03
Start Page: 3140
End Page: 3147
Language: English
DOI: 10.1021/acs.molpharmaceut.0c00437
PUBMED: 32644804
PROVIDER: scopus
PMCID: PMC7961817
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85089608863&doi=10.1021%2facs.molpharmaceut.0c00437&partnerID=40&md5=68636643b1c94dd85a4e924ab63c1eea
Notes: Article -- Export Date: 1 September 2020 -- Source: Scopus
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MSK Authors
  1. Kara Long Roche
    247 Long Roche
  2. Brian Zeglis
    118 Zeglis
  3. Jason S Lewis
    456 Lewis
  4. Sai Kiran Sharma
    25 Sharma
  5. Outi Maria Keinanen
    19 Keinanen
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