PET imaging with [11C]PBR28 can localize and quantify upregulated peripheral benzodiazepine receptors associated with cerebral ischemia in rat.
Peripheral benzodiazepine receptors (PBRs) are upregulated on activated microglia. We recently developed a promising positron emission tomography (PET) ligand, [11C]PBR28, with high affinity and excellent ratio of specific to nonspecific binding. We assessed the ability of [11C]PBR28 PET to localize PBRs in a rat permanent middle cerebral artery occlusion (MCAO) model of neuroinflammation. [11C]PBR28 was intravenously administered to rats at 4 and 7 days after permanent MCAO. In all experiments, arterial blood was sampled for compartmental modeling of regional distribution volumes, and rat brains were sampled after imaging for in vitro [3H]PK 11195 autoradiography and histological evaluation. [11C]PBR28 PET and [3H]PK 11195 autoradiography showed similar areas of increased PBRs, especially in the peri-ischemic core. Results from these in vivo and in vitro methods were strongly correlated. In this first study to demonstrate neuroinflammation in vivo with small animal PET, [11C]PBR28 had adequate sensitivity to localize and quantify the associated increase in PBRs.
Imaizumi
Masao
M
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 1, Room B3-10, 1 Center Drive, MSC 0135, Bethesda, MD 20892-0135, USA. imaizumim@intra.nimh.nih.gov
Kim
Hyun-Ju
HJ
Zoghbi
Sami S
SS
Briard
Emmanuelle
E
Hong
Jinsoo
J
Musachio
John L
JL
Ruetzler
Christl
C
Chuang
De-Maw
DM
Pike
Victor W
VW
Innis
Robert B
RB
Fujita
Masahiro
M
D000081:Acetamides / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography / Q000379:methods; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007546:Isoquinolines / Q000493:pharmacokinetics; D008297:Male; D010647:Phenyl Ethers / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D000081:Acetamides; D002247:Carbon Isotopes; C118942:DAA 1106; D007546:Isoquinolines; D010647:Phenyl Ethers; D011963:Receptors, GABA-A; C037850:PK 11195