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

• Main Authors: Dmitry M. Polikarpov, Douglas H. Campbell, Lucinda S. McRobb, Jiehua Wu, Maria E. Lund, Yanling Lu, Sergey M. Deyev, Andrew S. Davidson, Bradley J. Walsh, Andrei V. Zvyagin, David A. Gillatt
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Cancers
• Subjects: brain neoplasm; fluorescence-guided surgery; glypican-1; IRDye800CW; Miltuximab; monoclonal antibodies
• Online Access: https://www.mdpi.com/2072-6694/12/4/984

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 (<i>p</i> = 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.