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Abstract
Glioblastoma is the most common and fatal primary glioma and has a severe prognosis. It is a challenge for neurosurgeons to remove brain tumor tissues completely by resection. Meanwhile, fluorescence-guided surgery (FGS) is a technique used in glioma surgery to enhance the visualization of tumor edges to clarify the extent of tumor resection. Indocyanine green (ICG) is the only FDA-approved NIR fluorescent agent. It non-covalently binds to human serum albumin (HSA). Secreted protein acidic and rich in cysteine (SPARC) is an extracellular glycoprotein expressed in gliomas and binds to albumin, suggesting that it plays an important role in tumor uptake of the ICG-HSA complex. Here we demonstrate the binding properties of HSA or SPARC to ICG using surface plasmon resonance and saturation binding assay. According to in vitro and in vivo studies, the results showed that the uptake of ICG-HSA complex was higher in SPARC-expressing glioblastoma cell line and tumor region compared with the uptake of free ICG. Here, we visualized the SPARC-dependent uptake of ICG and ICG-HSA complex in U87MG. Our results demonstrated that the ICG-HSA complex is likely to be used as an efficient imaging agent targeting SPARC-expressing tumors, especially glioblastoma.

Affiliations

Hye Jung Jang 1 2 3, Myung Geun Song 1 4, Cho Rong Park 1, Hyewon Youn 1 3 5, Yun-Sang Lee 1 2 3 6, Gi Jeong Cheon 1 3, Keon Wook Kang 1 2 3 4 6
1Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
2Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Republic of Korea.
3Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
4Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea.
5Cancer Imaging Center, Seoul National University Hospital, Seoul 03080, Republic of Korea.
6Institute of Radiation Medicine, Medical Research Center, Seoul National University Hospital, Seoul 03080, Republic of Korea.