Near-Infrared Fluorescent Peptides with High Tumor Selectivity: Novel Probes for Image-Guided Surgical Resection of Orthotopic Glioma

The complete excision of glioblastomas with maximal retention of surrounding normal tissues can have a positive effect on the survival status and quality of life of patients. Near-infrared fluorescence (NIRF) optical imaging of the tumor vasculature offers a noninvasive method for detection of early stage glioblastoma and efficient monitoring of therapeutic responses. The aim of this study was to develop a novel NIRF imaging probe as a visualization tool for image-guided surgical resection of orthotopic glioblastoma. In this study, Cy5.5-RKL, Cy5.5-NKL, and Cy5.5-DKL probes were successfully synthesized, and their properties were investigated in vitro and in vivo. In vivo, Cy5.5-RKL and Cy5.5-NKL were able to detect U87MG xenografts for at least 8 h post injection. The maximum tumor-to-muscle ratios of Cy5.5-RKL and Cy5.5-NKL were 7.65 ± 0.72 and 5.43 ± 0.72, respectively. Of the probes, Cy5.5-RKL displayed the best delineation of the boundaries between orthotopic glioblastomas and normal brain tissue at 8 h p.i. In conclusion, NIRF imaging using Cy5.5-RKL is promising not only for diagnostic purposes but also for use in image-guided surgery for orthotopic glioblastoma or other superficial tumors.