@article{oai:repo.qst.go.jp:00047777, author = {JI, BIN and Kaneko, Hiroyuki and Minamimoto, Takafumi and Inoue, Haruhisa and Takeuchi, Hiroki and Kumata, Katsushi and Zhang, Ming-Rong and Aoki, Ichio and Seki, Chie and Ono, Maiko and Tokunaga, Masaki and Tsukamoto, Satoshi and Tanabe, Koji and Shin, Ryong-Moon and Minamihisamatsu, Takeharu and Kito, Seiji and J., Richmond Barry and Suhara, Tetsuya and Higuchi, Makoto and 季 斌 and 南本 敬史 and 熊田 勝志 and 張 明栄 and 青木 伊知男 and 関 千江 and 小野 麻衣子 and 徳永 正希 and 塚本 智史 and 南久松 丈晴 and 鬼頭 靖司 and 須原 哲也 and 樋口 真人}, issue = {45}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, month = {Nov}, note = {Chemogenetic manipulation of neuronal activities has been enabled by a designer receptor (DREADD) exclusively activated by clozapine-N-oxide (CNO). Here, we applied CNO as a functional reporter probe to positron emission tomography (PET) of DREADD in living brains. Mutant human M4 DREADD (hM4Di) expressed in transgenic mouse neurons was visualized by PET with microdose [11C]CNO. Deactivation of DREADD-expressing neurons in these mice by nonradioactive CNO at a pharmacological dose could also be captured by arterial spin labeling MRI (ASL-MRI). Neuroprogenitors derived from hM4Di transgenic-induced pluripotent stem cells (iPSCs) were then implanted into wild-type mouse brains, and neuronal differentiation of the grafts could be imaged by [11C]CNO-PET. Finally, ASL-MRI captured chemogenetic functional manipulation of the graft neurons. Our data provide the first demonstration of multimodal molecular/functional imaging of cells expressing a functional gene reporter in the brain, which would be translatable to humans for therapeutic gene transfers and cell replacements.}, pages = {11544--11558}, title = {Multimodal Imaging for DREADD-expressing Neurons in Living Brain and Their Application to Implantation of iPSC-derived Neural Progenitors}, volume = {36}, year = {2016} }