Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats.
[(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [(11)C]PK11195 signal are not well characterized. We performed [(11)C]PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [(3)H]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [(11)C]PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [(3)H]PK11195 binding increased at day 4, and increases further at day 7. The PET signal also augmented in peripheral regions, but to a lesser extent than in the core. Binding in the region surrounding infarction was supported by [(11)C]PK11195 autoradiography at day 7 showing that the radioactive signal extended beyond the infarcted core. Enhanced binding was preceded by increases in PBR mRNA expression in the ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed subsets of ameboid microglia/macrophages within the infarcted core showing a distinctive strong PBR expression from day 4. These cells were often located surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding infarction at day 7 also showed some PBR immunostaining. These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding depends on intrinsic features of the inflammatory cells.
Rojas
Santiago
S
Department of Brain Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona (IIBB)-Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Martín
Abraham
A
Arranz
Maria J
MJ
Pareto
Deborah
D
Purroy
Jesús
J
Verdaguer
Esther
E
Llop
Jordi
J
Gómez
Vanessa
V
Gispert
Joan D
JD
Millán
Olga
O
Chamorro
Angel
A
Planas
Anna M
AM
D000818:Animals; D001345:Autoradiography; D015153:Blotting, Western; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000473:pathology; D002544:Cerebral Infarction / Q000000981:diagnostic imaging / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007249:Inflammation / Q000000981:diagnostic imaging* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging* / Q000473:pathology; D007546:Isoquinolines; D008297:Male; D049268:Positron-Emission Tomography; D012333:RNA, Messenger / Q000096:biosynthesis; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000378:metabolism*; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000473:pathology
D007546:Isoquinolines; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; C037850:PK 11195