Evidence map›Paper›PMID 34636430›Full record

ArticleThe EMBO journal2021

A genetically targeted reporter for PET imaging of deep neuronal circuits in mammalian brains.

Masafumi Shimojo, Maiko Ono, Hiroyuki Takuwa, Koki Mimura, Yuji Nagai, Masayuki Fujinaga, Tatsuya Kikuchi, Maki Okada, Chie Seki, Masaki Tokunaga and 12 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 16 citations in OpenAlex.

  1. Dynamic alterations in the central glutamatergic status following food and glucose intake:Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
    Trial
  2. Article
  3. Article
  4. First-in-Human Biodistribution and Dosimetry of [Molecular imaging and biology · 2026
    Article
  5. Imaging-based whole brain-level neural circuit visualization.European journal of nuclear medicine and molecular imaging · 2025
    Article
  6. TRPC6 is a mechanosensitive channel essential for ultrasound neuromodulation in the mammalian brain.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. A genetically encoded protein tag for control and quantitative imaging of CAR T cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  8. PET reporter systems for the brain.Trends in neurosciences · 2023
    Review
  9. Review
  10. Reporter Genes for Brain Imaging Using MRI, SPECT and PET.International journal of molecular sciences · 2022
    Review
  11. Review
  12. Article
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 3 institutions in 2 countries.

Masafumi ShimojoDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.ORCID 0000-0003-4491-7294
Maiko OnoDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Hiroyuki TakuwaDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Koki MimuraDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Yuji NagaiDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Masayuki FujinagaDepartment of Radiopharmaceuticals Development, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Tatsuya KikuchiDepartment of Radiopharmaceuticals Development, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Maki OkadaDepartment of Radiopharmaceuticals Development, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Chie SekiDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.ORCID 0000-0002-3222-7125
Masaki TokunagaDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Jun MaedaDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Yuhei TakadoDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Manami TakahashiDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Takeharu MinamihisamatsuDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Ming-Rong ZhangDepartment of Radiopharmaceuticals Development, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Yutaka TomitaDepartment of Neurology, Keio University School of Medicine, Tokyo, Japan.
Norihiro SuzukiDepartment of Neurology, Keio University School of Medicine, Tokyo, Japan.
Anton MaximovDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
Tetsuya SuharaDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Takafumi MinamimotoDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.ORCID 0000-0003-4305-0174
Naruhiko SaharaDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Makoto HiguchiDepartment of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
National Institutes for Quantum Science and Technology · JPKeio University · JPScripps Research Institute · US

Funding

Transcriptional Control of Synaptic Plasticity by Class IIa HDACsR01NS087026 · NINDS · SCRIPPS RESEARCH INSTITUTE, THE · PI MAXIMOV, ANTON · 2015 to 2024
$5.4M
New approaches for chemical-genetic targeting of specific circuits and cell types in the mammalian brainRF1MH123224 · NIMH · SCRIPPS RESEARCH INSTITUTE, THE · PI MAXIMOV, ANTON · 2020 to 2020
$2.7M
NIMH NIH HHS RF1 MH123224NINDS NIH HHS R01 NS087026
6 · The paper itself

Abstract

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.

Indexed as

AnimalsBrainCallithrixCarbon RadioisotopesFluorine RadioisotopesGenes, ReporterHEK293 CellsHumansMaleMiceMice, Inbred C57BLMolecular ImagingNerve NetPositron-Emission TomographyProteinsRadiopharmaceuticalsCarbon-11Carbon RadioisotopesFluorine-18Fluorine RadioisotopesProteinsRadiopharmaceuticalsTetrahydrofolate DehydrogenaseTrimethoprimfluorescenceneural circuitnon-invasivePETreporter imaging

Identifiers

PMID34636430
PMCPMC8591537
OpenAlexW3205864048

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.