Imaging of reactive oxygen species in focal ischemic mouse brain using a radical trapping tracer [3H]hydromethidine

Koji Abe, Misato Tonomura, Miwa Ito, Nozomi Takai, Natsumi Imamoto, Takemi Rokugawa, Sotaro Momosaki, Kazumi Fukumoto, Kenji Morimoto, Osamu Inoue

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Reactive oxygen species (ROS) have been implicated in the pathophysiology of the brain after ischemic stroke. In this study, we investigate the generation of brain ROS after transient focal ischemia in mice using a radical trapping radiotracer, [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]hydromethidine), which we recently reported as a ROS imaging probe. We also examined the effect of dimethylthiourea (DMTU), a hydroxyl radical scavenger, on brain ROS generation and infarct volume after transient focal ischemia in mice. Methods: [3H]Hydromethidine was intravenously injected into mice at 1, 2, 5, and 7 h after transient middle cerebral artery occlusion (tMCAO), and then, the brain autoradiogram was acquired at 60 min after tracer injection. Brain infarct volumes at 24 h after tMCAO were assessed by 2,3,5-triphenyltetrazolium chloride staining. Results: Accumulation of radioactivity was observed in the ipsilateral striatum and cortex at 1 h after tMCAO. The increase of radioactivity was attenuated at 2 h after tMCAO and then became maximized at 5 h. The high accumulation of radioactivity remained until 7 h after tMCAO. DMTU treatment significantly attenuated the accumulation of radioactivity in the ipsilateral hemisphere at 1, 5, and 7 h after tMCAO. Brain infarct volumes were also significantly reduced in DMTU-treated mice at 24 h after tMCAO. Conclusions: These results indicated that [3H]hydromethidine is a useful radiotracer for detecting in vivo brain ROS generation such as hydroxyl radical after ischemic injury.

Original languageEnglish
Article number37
JournalEJNMMI Research
Volume5
Issue number1
DOIs
Publication statusPublished - Dec 29 2015
Externally publishedYes

Fingerprint

Middle Cerebral Artery Infarction
Reactive Oxygen Species
Brain
Radioactivity
Hydroxyl Radical
Ischemia
N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine
Stroke
Staining and Labeling
Injections
Wounds and Injuries
1,3-dimethylthiourea

Keywords

  • Cerebral ischemia
  • Middle cerebral artery occlusion
  • Reactive oxygen species

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Imaging of reactive oxygen species in focal ischemic mouse brain using a radical trapping tracer [3H]hydromethidine. / Abe, Koji; Tonomura, Misato; Ito, Miwa; Takai, Nozomi; Imamoto, Natsumi; Rokugawa, Takemi; Momosaki, Sotaro; Fukumoto, Kazumi; Morimoto, Kenji; Inoue, Osamu.

In: EJNMMI Research, Vol. 5, No. 1, 37, 29.12.2015.

Research output: Contribution to journalArticle

Abe, K, Tonomura, M, Ito, M, Takai, N, Imamoto, N, Rokugawa, T, Momosaki, S, Fukumoto, K, Morimoto, K & Inoue, O 2015, 'Imaging of reactive oxygen species in focal ischemic mouse brain using a radical trapping tracer [3H]hydromethidine', EJNMMI Research, vol. 5, no. 1, 37. https://doi.org/10.1186/s13550-015-0115-1
Abe, Koji ; Tonomura, Misato ; Ito, Miwa ; Takai, Nozomi ; Imamoto, Natsumi ; Rokugawa, Takemi ; Momosaki, Sotaro ; Fukumoto, Kazumi ; Morimoto, Kenji ; Inoue, Osamu. / Imaging of reactive oxygen species in focal ischemic mouse brain using a radical trapping tracer [3H]hydromethidine. In: EJNMMI Research. 2015 ; Vol. 5, No. 1.
@article{b23e1be3f5b445a780fee4683305158e,
title = "Imaging of reactive oxygen species in focal ischemic mouse brain using a radical trapping tracer [3H]hydromethidine",
abstract = "Background: Reactive oxygen species (ROS) have been implicated in the pathophysiology of the brain after ischemic stroke. In this study, we investigate the generation of brain ROS after transient focal ischemia in mice using a radical trapping radiotracer, [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]hydromethidine), which we recently reported as a ROS imaging probe. We also examined the effect of dimethylthiourea (DMTU), a hydroxyl radical scavenger, on brain ROS generation and infarct volume after transient focal ischemia in mice. Methods: [3H]Hydromethidine was intravenously injected into mice at 1, 2, 5, and 7 h after transient middle cerebral artery occlusion (tMCAO), and then, the brain autoradiogram was acquired at 60 min after tracer injection. Brain infarct volumes at 24 h after tMCAO were assessed by 2,3,5-triphenyltetrazolium chloride staining. Results: Accumulation of radioactivity was observed in the ipsilateral striatum and cortex at 1 h after tMCAO. The increase of radioactivity was attenuated at 2 h after tMCAO and then became maximized at 5 h. The high accumulation of radioactivity remained until 7 h after tMCAO. DMTU treatment significantly attenuated the accumulation of radioactivity in the ipsilateral hemisphere at 1, 5, and 7 h after tMCAO. Brain infarct volumes were also significantly reduced in DMTU-treated mice at 24 h after tMCAO. Conclusions: These results indicated that [3H]hydromethidine is a useful radiotracer for detecting in vivo brain ROS generation such as hydroxyl radical after ischemic injury.",
keywords = "Cerebral ischemia, Middle cerebral artery occlusion, Reactive oxygen species",
author = "Koji Abe and Misato Tonomura and Miwa Ito and Nozomi Takai and Natsumi Imamoto and Takemi Rokugawa and Sotaro Momosaki and Kazumi Fukumoto and Kenji Morimoto and Osamu Inoue",
year = "2015",
month = "12",
day = "29",
doi = "10.1186/s13550-015-0115-1",
language = "English",
volume = "5",
journal = "EJNMMI Research",
issn = "2191-219X",
publisher = "Springer Berlin",
number = "1",

}

TY - JOUR

T1 - Imaging of reactive oxygen species in focal ischemic mouse brain using a radical trapping tracer [3H]hydromethidine

AU - Abe, Koji

AU - Tonomura, Misato

AU - Ito, Miwa

AU - Takai, Nozomi

AU - Imamoto, Natsumi

AU - Rokugawa, Takemi

AU - Momosaki, Sotaro

AU - Fukumoto, Kazumi

AU - Morimoto, Kenji

AU - Inoue, Osamu

PY - 2015/12/29

Y1 - 2015/12/29

N2 - Background: Reactive oxygen species (ROS) have been implicated in the pathophysiology of the brain after ischemic stroke. In this study, we investigate the generation of brain ROS after transient focal ischemia in mice using a radical trapping radiotracer, [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]hydromethidine), which we recently reported as a ROS imaging probe. We also examined the effect of dimethylthiourea (DMTU), a hydroxyl radical scavenger, on brain ROS generation and infarct volume after transient focal ischemia in mice. Methods: [3H]Hydromethidine was intravenously injected into mice at 1, 2, 5, and 7 h after transient middle cerebral artery occlusion (tMCAO), and then, the brain autoradiogram was acquired at 60 min after tracer injection. Brain infarct volumes at 24 h after tMCAO were assessed by 2,3,5-triphenyltetrazolium chloride staining. Results: Accumulation of radioactivity was observed in the ipsilateral striatum and cortex at 1 h after tMCAO. The increase of radioactivity was attenuated at 2 h after tMCAO and then became maximized at 5 h. The high accumulation of radioactivity remained until 7 h after tMCAO. DMTU treatment significantly attenuated the accumulation of radioactivity in the ipsilateral hemisphere at 1, 5, and 7 h after tMCAO. Brain infarct volumes were also significantly reduced in DMTU-treated mice at 24 h after tMCAO. Conclusions: These results indicated that [3H]hydromethidine is a useful radiotracer for detecting in vivo brain ROS generation such as hydroxyl radical after ischemic injury.

AB - Background: Reactive oxygen species (ROS) have been implicated in the pathophysiology of the brain after ischemic stroke. In this study, we investigate the generation of brain ROS after transient focal ischemia in mice using a radical trapping radiotracer, [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]hydromethidine), which we recently reported as a ROS imaging probe. We also examined the effect of dimethylthiourea (DMTU), a hydroxyl radical scavenger, on brain ROS generation and infarct volume after transient focal ischemia in mice. Methods: [3H]Hydromethidine was intravenously injected into mice at 1, 2, 5, and 7 h after transient middle cerebral artery occlusion (tMCAO), and then, the brain autoradiogram was acquired at 60 min after tracer injection. Brain infarct volumes at 24 h after tMCAO were assessed by 2,3,5-triphenyltetrazolium chloride staining. Results: Accumulation of radioactivity was observed in the ipsilateral striatum and cortex at 1 h after tMCAO. The increase of radioactivity was attenuated at 2 h after tMCAO and then became maximized at 5 h. The high accumulation of radioactivity remained until 7 h after tMCAO. DMTU treatment significantly attenuated the accumulation of radioactivity in the ipsilateral hemisphere at 1, 5, and 7 h after tMCAO. Brain infarct volumes were also significantly reduced in DMTU-treated mice at 24 h after tMCAO. Conclusions: These results indicated that [3H]hydromethidine is a useful radiotracer for detecting in vivo brain ROS generation such as hydroxyl radical after ischemic injury.

KW - Cerebral ischemia

KW - Middle cerebral artery occlusion

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=84938268266&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938268266&partnerID=8YFLogxK

U2 - 10.1186/s13550-015-0115-1

DO - 10.1186/s13550-015-0115-1

M3 - Article

AN - SCOPUS:84938268266

VL - 5

JO - EJNMMI Research

JF - EJNMMI Research

SN - 2191-219X

IS - 1

M1 - 37

ER -