In vivo imaging of microglial activation using a peripheral benzodiazepine receptor ligand: [11C]PK-11195 and animal PET following ethanol injury in rat striatum.
OBJECTIVE
To investigate whether [(11)C]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 [(11)C]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 [(11)C]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 (V (60)) as an estimate of V. On the coronal PET image, ROIs were placed on bilateral ST. Differences in right/left ST V (60) 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 [(11)C]PK-11195 PET imaging would be a useful tool for evaluating microglial activation in a rat brain injury model.
Toyama
Hiroshi
H
Department of Radiology, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan. htoyama@fujita-hu.ac.jp
Hatano
Kentaro
K
Suzuki
Hiromi
H
Ichise
Masanori
M
Momosaki
Sotaro
S
Kudo
Gen
G
Ito
Fumitaka
F
Kato
Takashi
T
Yamaguchi
Hiroshi
H
Katada
Kazuhiro
K
Sawada
Makoto
M
Ito
Kengo
K
D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol; D007546:Isoquinolines / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D017628:Microglia / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000662:veterinary*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D011963:Receptors, GABA-A / Q000378:metabolism*; D014018:Tissue Distribution
D002352:Carrier Proteins; D007546:Isoquinolines; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D000431:Ethanol; C037850:PK 11195