@article{oai:repo.qst.go.jp:00084657, author = {Shimojo, Masafumi and Ono, Maiko and Takuwa, Hiroyuki and Mimura, Koki and Nagai, Yuji and Fujinaga, Masayuki and Kikuchi, Tatsuya and Okada, Maki and Seki, Chie and Tokunaga, Masaki and Maeda, Jun and Takado, Yuhei and Takahashi, Manami and Minamihisamatsu, Takeharu and Ming-Rong, Zhang and Tomita, Yutaka and Suzuki, Norihiro and Maximov, Anton and Suhara, Tetsuya and Minamimoto, Takafumi and Sahara, Naruhiko and Higuchi, Makoto and Masafumi, Shimojo and Maiko, Ono and Hiroyuki, Takuwa and Koki, Mimura and Yuji, Nagai and Masayuki, Fujinaga and Tatsuya, Kikuchi and Maki, Okada and Chie, Seki and Masaki, Tokunaga and Jun, Maeda and Yuhei, Takado and Takahashi, Manami and Takeharu, Minamihisamatsu and Zhang, Ming-Rong and Tetsuya, Suhara and Takafumi, Minamimoto and Naruhiko, Sahara and Makoto, Higuchi}, issue = {22}, journal = {The EMBO Journal}, month = {Oct}, note = {Positron emission tomography (PET) allows biomolecular tracking but PET monitoring of brain networks has been hampered by a lack of suitable reporters. Here, we take advantage of bacterial dihydrofolate reductase, ecDHFR, and its unique antagonist, TMP, to facilitate in vivo imaging in the brain. Peripheral administration of radiofluorinated and fluorescent TMP analogs enabled PET and intravital microscopy, respectively, of neuronal ecDHFR expression in mice. This technique can be used to the visualize neuronal circuit activity elicited by chemogenetic manipulation in the mouse hippocampus. Notably, ecDHFR-PET allows mapping of neuronal projections in non-human primate brains, demonstrating the applicability of ecDHFR-based tracking technologies for network monitoring. Finally, we demonstrate the utility of TMP analogs for PET studies of turnover and self-assembly of proteins tagged with ecDHFR mutants. These results establish opportunities for a broad spectrum of previously unattainable PET analyses of mammalian brain circuits at the molecular level.}, title = {A genetically targeted reporter for PET imaging of deep neuronal circuits in mammalian brains}, volume = {40}, year = {2021} }