Reduced PBR/TSPO expression after minocycline treatment in a rat model of focal cerebral ischemia: a PET study using [(18)F]DPA-714.
BACKGROUND
Many new candidate pharmaceuticals designed to improve recovery after stroke have been proposed recently, but there are still too few molecular imaging methods capable to assess their efficacy. A hallmark of the inflammatory reaction that follows focal cerebral ischemia is overexpression of the mitochondrial peripheral benzodiazepine receptor/18 kDa translocator protein (PBR/TSPO) in the monocytic lineage and astrocytes. This overexpression can be imaged with positron emission tomography (PET) using PBR/TSPO-selective radioligands such as [(18)F]DPA-714.


OBJECTIVE
Here, we tested whether PET with [(18)F]DPA-714 would evidence the effect of minocycline, a broad spectrum antibiotic presently tested as neuroprotective agent after stroke, on the inflammatory reaction induced in an experimental model of stroke.


METHODS
Ten rats were subjected to a 2-h transient middle cerebral artery occlusion with reperfusion. Minocycline or saline was intravenously administrated 1 h after reperfusion and daily during the following 6 days. PET studies were performed using [(18)F]DPA-714 at 7 days after cerebral ischemia.


RESULTS
In vivo PET imaging showed a significant decrease in [(18)F]DPA-714 uptake at 7 days after cerebral ischemia in rats treated with minocycline with respect to saline-treated animals. Minocycline treatment had no effect on the size of the infarcted area.


CONCLUSIONS
Minocycline administered daily during 7 days after ischemia decreases [(18)F]DPA-714 binding, suggesting that the drug exerts an anti-inflammatory activity. [(18)F]DPA-714 PET is a useful biomarker to study novel anti-inflammatory strategies in experimental cerebral ischemia.
Martín
Abraham
A
CEA, DSV, I²BM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale, INSERM U803, 4 Place Géneral Leclerc, 91406 Orsay Cedex, France.
Boisgard
Raphaël
R
Kassiou
Michael
M
Dollé
Frédéric
F
Tavitian
Bertrand
B
D000818:Animals; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism*; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes / Q000378:metabolism*; D008297:Male; D008911:Minocycline / Q000008:administration & dosage*; D011720:Pyrazoles; D011743:Pyrimidines; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism
D005462:Fluorine Radioisotopes; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; D008911:Minocycline
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