@article{oai:repo.qst.go.jp:00073849,
 author = {大島, 康宏 and 河野, 暢明 and 横田, 裕一郎 and 渡辺, 茂樹 and 佐々木, 一郎 and 石岡, 典子 and 坂下, 哲哉 and 荒川, 和晴 and Oshima, Yasuhiro and Yokota, Yuuichiro and Watanabe, Shigeki and Sasaki, Ichiro and Ishioka, Noriko and Sakashita, Tetsuya},
 issue = {6},
 journal = {Theranostics},
 month = {Mar},
 note = {Targeted α-particle therapy is a promising option for patients with malignant pheochromocytoma. Recent observations regarding meta-211At-astato-benzylguanidine (211At-MABG) in a pheochromocytoma mouse model showed a strong anti-tumor effect, though the molecular mechanism remains elusive. Here, we present the first comprehensive RNA-sequencing (RNA-seq) data for pheochromocytoma cells based on in vitro 211At-MABG administration experiments. Key genes and pathways in the tumor α-particle radiation response are also examined to obtain potential response biomarkers.
Methods: We evaluated genome-wide transcriptional alterations in the rat pheochromocytoma cell line PC12 at 3, 6, and 12 h after 211At-MABG treatment; a control experiment using 60Co γ-ray irradiation was carried out to highlight 211At-MABG-specific gene expression. For comparisons, 10% and 80% iso-survival doses (0.8 and 0.1 kBq/mL for 211At-MABG and 10 and 1 Gy for 60Co γ-rays) were used.
Results: Enrichment analysis of differentially expressed genes (DEGs) and analysis of the gene expression profiles of cell cycle checkpoints revealed similar modes of cell death via the p53-p21 signaling pathway after 211At-MABG treatment and γ-ray irradiation. The top list of ranked DEGs demonstrated the expression of key genes on the decrease in the survival following 211At-MABG exposure, and four potential genes (Mien1, Otub1, Vdac1 and Vegfa genes) of 211At-MABG therapy. Western blot analysis indicated increased expression of TSPO in 211At-MABG-treated cells, suggesting its potential as a PET imaging probe.
Conclusion: Comprehensive RNA-seq revealed contrasting cellular responses to γ-ray and α-particle therapy, leading to the identification of four potential candidate genes that may serve as molecular imaging and 211At-MABG therapy targets.},
 title = {Anti-tumor effects and potential therapeutic response biomarkers in alpha-emitting meta-At-211-astato-benzylguanidine therapy for malignant pheochromocytoma explored by RNA-sequencing},
 volume = {9},
 year = {2019}
}