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Open AccessArticle

Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab®-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery

1
Department of Clinical Medicine, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW 2109, Australia
2
Glytherix Ltd., Sydney, NSW 2113, Australia
3
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, Russia
4
ARC Centre of Excellence for Nanoscale BioPhotonics, Macquarie University, Sydney, NSW 2109, Australia
5
Institute of Molecular Medicine, Sechenov University, 119991 Moscow, Russia
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(4), 984; https://doi.org/10.3390/cancers12040984
Received: 13 March 2020 / Revised: 7 April 2020 / Accepted: 12 April 2020 / Published: 16 April 2020
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. View Full-Text
Keywords: brain neoplasm; fluorescence-guided surgery; glypican-1; IRDye800CW; Miltuximab; monoclonal antibodies; molecular imaging brain neoplasm; fluorescence-guided surgery; glypican-1; IRDye800CW; Miltuximab; monoclonal antibodies; molecular imaging
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Polikarpov, D.M.; Campbell, D.H.; McRobb, L.S.; Wu, J.; Lund, M.E.; Lu, Y.; Deyev, S.M.; Davidson, A.S.; Walsh, B.J.; Zvyagin, A.V.; Gillatt, D.A. Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab®-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery. Cancers 2020, 12, 984.

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