Journal
JOURNAL OF NEURO-ONCOLOGY
Volume 148, Issue 2, Pages 245-258Publisher
SPRINGER
DOI: 10.1007/s11060-020-03527-3
Keywords
Transferrin receptor 1; Near-infrared fluorescence imaging; Glioblastoma; Molecular imaging; Fluorescence-guided surgery
Categories
Funding
- National Basic Research Program (973) [2015CB755505]
- National Natural Science Foundation of China (NSFC) [81372685, 81872059, 81572479, 81772677]
- Guangzhou Science Technology and Innovation Project [201508020125]
- Science and Technology Planning Project [2016A020213004]
- Natural Science Foundation of Guangdong Province (NSFG) [2016A030313309]
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Objective Optical molecular imaging technology that indiscriminately detects intracranial glioblastoma (GBM) can help neurosurgeons effectively remove tumor masses. Transferrin receptor 1 (TfR 1) is a diagnostic and therapeutic target in GBM. A TfR 1-targeted peptide, CRTIGPSVC (CRT), was shown to cross the blood brain barrier (BBB) and accumulate at high levels in GBM tissues. In this study, we synthesized a TfR 1-targeted near-infrared fluorescent (NIRF) probe, Cy5-CRT, for identifying the GBM tissue margin in mouse models. Methods We initially confirmed the overexpression of TfR 1 in GBM and the tumor-specific homing ability of Cy5-CRT in subcutaneous and orthotopic GBM mouse models. We then examined the feasibility of Cy5-CRT for identifying the tumor margin in orthotopic GBM xenografts. Finally, we compared Cy5-CRT with the clinically used fluorescein sodium in identifying tumor margins. Results Cy5-CRT specifically accumulated in GBM tissues and detected the tumor burden with exceptional contrast in mice with orthotopic GBM, enabling fluorescence-guided GBM resection under NIRF live imaging conditions. Importantly, Cy5-CRT recognized the GBM tissue margin more clearly than fluorescein sodium. Conclusions The TfR 1-targeted optical probe Cy5-CRT specifically differentiates tumor tissues from the surrounding normal brain with high sensitivity, indicating its potential application for the precise surgical removal of GBM.
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