Near-infrared molecular imaging of glioblastoma by Miltuximab®-IRDye800CW as a potential tool for fluorescence-guided surgery

Dmitry Polikarpov*, Douglas H. Campbell, Lucinda McRobb, Jiehua Wu, Maria E. Lund, Yanling Lu, Sergey M. Deyev, Andrew S. Davidson, Bradley J. Walsh, Andrei Zvyagin, David Gillatt

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Glioblastoma (GBM) is one of the most aggressive tumors and its 5-year survival is approximately 5%. Fluorescence-guided surgery (FGS) improves the extent of resection and leads to better prognosis. Molecular near-infrared (NIR) imaging appears to outperform conventional FGS, however, novel molecular targets need to be identified in GBM. Proteoglycan glypican-1 (GPC-1) is believed to be such a target as it is highly expressed in GBM and is associated with poor prognosis. We hypothesize that an anti-GPC-1 antibody, Miltuximab®, conjugated with the NIR dye, IRDye800CW (IR800), can specifically accumulate in a GBM xenograft and provide high-contrast in vivo fluorescent imaging in rodents following systemic administration. Miltuximab® was conjugated with IR800 and intravenously administered to BALB/c nude mice bearing a subcutaneous U-87 GBM hind leg xenograft. Specific accumulation of Miltuximab®-IR800 in subcutaneous xenograft tumor was detected 24 h later using an in vivo fluorescence imager. The conjugate did not cause any adverse events in mice and caused strong fluorescence of the tumor with tumor-to-background ratio (TBR) reaching 10.1 ± 2.8. The average TBR over the 10-day period was 5.8 ± 0.6 in mice injected with Miltuximab®-IR800 versus 2.4 ± 0.1 for the control group injected with IgG-IR800 (p = 0.001). Ex vivo assessment of Miltuximab®-IR800 biodistribution confirmed its highly specific accumulation in the tumor. The results of this study confirm that Miltuximab®-IR800 holds promise for intraoperative fluorescence molecular imaging of GBM and warrants further studies.
Original languageEnglish
Article number984
Pages (from-to)1-14
Number of pages14
JournalCancers
Volume12
Issue number4
DOIs
Publication statusPublished - 16 Apr 2020

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • brain neoplasm
  • fluorescence-guided surgery
  • glypican-1
  • IRDye800CW
  • Miltuximab
  • monoclonal antibodies
  • molecular imaging

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