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Evaluation of the PBR/TSPO radioligand [18F]DPA-714 in a rat model of focal cerebral ischemia.
- Source :
- Journal of Cerebral Blood Flow & Metabolism; Jan2010, Vol. 30 Issue 1, p230-241, 12p, 1 Color Photograph, 1 Diagram, 5 Graphs
- Publication Year :
- 2010
-
Abstract
- Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed in vivo PET imaging with [<superscript>18</superscript>F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats. In vivo PET imaging showed significant increase in DPA (N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) uptake on the injured side compared with that in the contralateral area on days 7, 11, 15, and 21 after ischemia; the maximal binding value was reached 11 days after ischemia. In vitro autoradiography confirmed these in vivo results. In vivo and in vitro [<superscript>18</superscript>F]DPA-714 binding was displaced from the lesion by PK11195 and DPA-714. Immunohistochemistry showed increased PBR/TSPO expression, peaking at day 11 in cells expressing microglia/macrophage antigens in the ischemic area. At later times, a centripetal migration of astrocytes toward the lesion was observed, promoting the formation of an astrocytic scar. These results show that [<superscript>18</superscript>F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0271678X
- Volume :
- 30
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Journal of Cerebral Blood Flow & Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 47236933
- Full Text :
- https://doi.org/10.1038/jcbfm.2009.205