Abstract
Abstract Aptamers are synthetic single-stranded DNA or RNA that can be held together with complementary sequences by base-pairing. Tenascin-C is an extracellular matrix protein that is overexpressed in cancer tissues. Herein, we investigate the biological characteristics of Tenascin-C aptamer as potential tumor imaging agents. Cy5 or F-18 labeled Tenascin-C aptamers were prepared through hybridization-based labeling method using complementary oligonucleotide platform. Immunoblot analysis was performed on U-251 MG, U-87 MG, C6 and NCI-H460 cell lines to confirm the expression of tenascin-C. In vitro binding specificity of Tenascin-C aptamers was evaluated using confocal microscopy. In vivo biodistribution properties and PET Imaging of the 18F-labeled Tenascin-C were determined in C6 tumor-bearing nude mice. High levels of tenascin-C protein were detected in C6, U-251 MG. and U-87 MG cell lines. However, tenascin-C protein levels were undetectable in NCI-H460 cells. Confocal fluorescence microscopy images showed that Cy5-labeled Tenascin-C aptamer bound specifically to tenascin-C protein expressing cell lines including C6, U-251 MG and U-87 MG, however, not bound to NCI-H460 cells. Tumor uptake of 18F-labeled Tenascin-C aptamer was 1.64 ± 0.36 at 30 min after injection in C6 tumor xenografts. C6 tumors were clearly visualized by microPET imaging in a tumor-bearing mouse at 60 after injection. Tenascin-C aptamer was successfully labeled with F-18 labeled complementary oligonucleotide by base-pair hybridization. In vitro data showed that the cODN platform-hybridized Tenascin-C aptamer was selectively bound to target tumor cells. In addition, C6 tumor xenografts in mice were clearly visualized on microPET imaging. Our study demonstrated that Tenascin-C may be a useful target molecule for the imaging of malignant gliomas. Citation Format: Jun Young Park, Ye Lim Cho, Ju Ri Chae, Ga Eul Chu, Won Gil Cho, Sang Wun Kim, Won Jun Kang. Development and application of 18F-labeled Tenascin-C aptamer for cancer imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4114.
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