TY - JOUR
T1 - In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand
T2 - [11C]PK-11195 and animal PET following ethanol injury in rat striatum
AU - Toyama, Hiroshi
AU - Hatano, Kentaro
AU - Suzuki, Hiromi
AU - Ichise, Masanori
AU - Momosaki, Sotaro
AU - Kudo, Gen
AU - Ito, Fumitaka
AU - Kato, Takashi
AU - Yamaguchi, Hiroshi
AU - Katada, Kazuhiro
AU - Sawada, Makoto
AU - Ito, Kengo
N1 - Funding Information:
Acknowledgments We thank Mr. Junichiro Abe, Department of Brain Science and Molecular Imaging, National Institute for Longevity Sciences, Obu, Japan, for running the cyclotron. We appreciate Mr. Masao Ohashi, RT and other radiological technologists for running the MRI scanner and valuable suggestions.This research was supported in part by Japan Society for the Promotion of Science (JSPS) KAKENHI (18591369), the 21st Century COE (Center of Excellence) Medical Program (Development Center for Targeted and Minimally Invasive Diagnosis and Treatment) from JSPS and a grant from Fujita Health University and Suzuken Memorial Foundation.
PY - 2008/6
Y1 - 2008/6
N2 - Objective: To investigate whether [11C]PK-11195, a specific peripheral benzodiazepine receptors (PBRs) ligand for positron emission tomography (PET), can show activated microglia in a rat brain injury model. Methods: On day 1, ethanol was injected into the rat's right striatum (ST) using a stereotaxic operative procedure. On day 3, head magnetic resonance imaging (MRI) scans for surgically treated rats were performed to evaluate ethanol injury morphologically. On day 4, dynamic PET scans (17 injured rats and 7 non-injured controls) were performed for 60 min with an animal PET scanner under chloral hydrate anesthesia following a bolus injection of [11C]PK- 11195 through tail vein. Because PBRs are present throughout the brain, there is no suitable receptor-free reference region. The reference tissue model may not be applicable because of low target to background ratio for low affinity of [11C]PK-11195 to PBRs. We evaluated the PBRs binding with regions of interest (ROIs)-based approach to estimate total distribution volume (V). We used an integral from 0 min to 60 min (V60) as an estimate of V. On the coronal PET image, ROIs were placed on bilateral ST. Differences in right/left ST V60 ratios between lesioned and unlesioned control rats were compared using unpaired t tests. Immunohistochemical staining was performed for confirming the presence of activated microglia following decapitation on the PET experiment day. Results: The right/left ST V 60 ratios in lesioned rats (1.07 ± 0.08) were significantly higher than those in unlesioned control rats (1.00 ± 0.06, P < 0.05). On immunohistochemical staining, activated microglia were exclusively observed in the injured right ST but not in the noninjured left ST of the injury rats and the bilateral ST of the non-injured control rats. Conclusions: These results suggest that [11C]PK-11195 PET imaging would be a useful tool for evaluating microglial activation in a rat brain injury model.
AB - Objective: To investigate whether [11C]PK-11195, a specific peripheral benzodiazepine receptors (PBRs) ligand for positron emission tomography (PET), can show activated microglia in a rat brain injury model. Methods: On day 1, ethanol was injected into the rat's right striatum (ST) using a stereotaxic operative procedure. On day 3, head magnetic resonance imaging (MRI) scans for surgically treated rats were performed to evaluate ethanol injury morphologically. On day 4, dynamic PET scans (17 injured rats and 7 non-injured controls) were performed for 60 min with an animal PET scanner under chloral hydrate anesthesia following a bolus injection of [11C]PK- 11195 through tail vein. Because PBRs are present throughout the brain, there is no suitable receptor-free reference region. The reference tissue model may not be applicable because of low target to background ratio for low affinity of [11C]PK-11195 to PBRs. We evaluated the PBRs binding with regions of interest (ROIs)-based approach to estimate total distribution volume (V). We used an integral from 0 min to 60 min (V60) as an estimate of V. On the coronal PET image, ROIs were placed on bilateral ST. Differences in right/left ST V60 ratios between lesioned and unlesioned control rats were compared using unpaired t tests. Immunohistochemical staining was performed for confirming the presence of activated microglia following decapitation on the PET experiment day. Results: The right/left ST V 60 ratios in lesioned rats (1.07 ± 0.08) were significantly higher than those in unlesioned control rats (1.00 ± 0.06, P < 0.05). On immunohistochemical staining, activated microglia were exclusively observed in the injured right ST but not in the noninjured left ST of the injury rats and the bilateral ST of the non-injured control rats. Conclusions: These results suggest that [11C]PK-11195 PET imaging would be a useful tool for evaluating microglial activation in a rat brain injury model.
KW - Animal PET
KW - Microglia
KW - Peripheral benzodiazepine receptors
KW - Rat
KW - [C]PK-11195
UR - https://www.scopus.com/pages/publications/46649095233
UR - https://www.scopus.com/pages/publications/46649095233#tab=citedBy
U2 - 10.1007/s12149-008-0136-1
DO - 10.1007/s12149-008-0136-1
M3 - Article
C2 - 18600420
AN - SCOPUS:46649095233
SN - 0914-7187
VL - 22
SP - 417
EP - 424
JO - Annals of Nuclear Medicine
JF - Annals of Nuclear Medicine
IS - 5
ER -