Article Figures & Data
Figures
- FIGURE 1.
Synthesis of (R)- and (S)-11C-KTP-Me via rapid C-11C-methylation and chiral resolution.
- FIGURE 2.
Representative PET images and time–radioactivity curves of each 11C-KTP-Me enantiomer in rat brain after lipopolysaccharide injection. (A) Transaxial rat brain views of SUV-summed PET images from 5 to 45 min after tracer injection were coregistered with individual MR images at baseline. (S)-11C-KTP-Me showed higher accumulation and superior specificity in rat brain hemisphere than (RS)- and (R)-11C-KTP-Me. (B) Quantitative time–radioactivity curves of each 11C-KTP-Me enantiomer in contralateral (Contra) and ipsilateral (Ipsi) striatum. Data are expressed as SUV and are mean ± SD ((R)-[11C]KTP-Me, n = 3; others, n = 4).
- FIGURE 3.
Age-dependent changes in (S)-11C-KTP-Me accumulation in brain of APP-Tg 2576 and wild-type mice. Representative ex vivo autoradiographs of coronal sections of mice at 15 min after PET tracer injection. Progressive and remarkable increases in (S)-11C-KTP-Me in frontal cortex, parietal occipital cortex, and hippocampus of APP-Tg mice from 16 mo old. Range bar represents intensity of photostimulated luminescence (PSL/mm2).
- FIGURE 4.
Age-dependent changes in regional brain uptake of (S)-11C-KTP-Me in APP-Tg 2576 and wild-type mice obtained from quantification of ex vivo autoradiography. Significant increases in (S)-11C-KTP-Me accumulation in APP-Tg mice are shown in all brain regions at 16 and 24 mo old compared with wild-type mice. Data are expressed as percentage injected dose per gram (%ID/g) and are mean ± SD (8 mo, n = 3; 13 and 24 mo, n = 4; 16 mo, n = 5). *P < 0.05, frontal cortex of APP-Tg mice vs. wild-type mice. ††P < 0.01, parietal cortex of APP-Tg mice vs. wild-type mice. ‡‡P < 0.01, hippocampus of APP-Tg mice vs. wild-type mice. §P < 0.05, cerebellum of APP-Tg mice vs. wild-type mice. CERE = cerebellum; F-CTX = frontal cortex; HIP = hippocampus; P-CTX = parietal cortex; STR = striatum.
- FIGURE 5.
Age-dependent correlation between COX-1–expressing activated microglia and Aβ plaque formation in APP-Tg 2576 mouse brain. Representative photomicrographs of triple immunofluorescent labeling for Aβ1–16 (red), CD11b (blue), and COX-1 (green) in hippocampus of APP-Tg mice at 8, 13, 16, and 24 mo old. Arrows indicate cells coexpressing CD11b and COX-1. Population and fluorescence intensity of COX-1–expressing CD11b-positive activated microglia showed age-dependent increase from 16 mo old, which was well correlated with formation of Aβ oligomers.
Tables
- TABLE 1
Inhibitory Effects of Ketoprofen Enantiomers on Ovine COX-1 and COX-2 Activities (IC50, μM)
Substrate (RS)-ketoprofen (R)-ketoprofen (S)-ketoprofen COX-1 0.031 126.7 0.011 COX-2 1.04 470.7 0.195 - TABLE 2
Regional Brain Accumulation of 11C-KTP-Me Enantiomers in Rat Brain After Intrastriatal Injection of Lipopolysaccharide
Region (RS)-11C-KTP-Me (R)-11C-KTP-Me (S)-11C-KTP-Me Ipsilateral striatum 1.14 ± 0.101 0.79 ± 0.145* 1.70 ± 0.092† Contralateral striatum 0.30 ± 0.019 0.20 ± 0.009 0.34 ± 0.031 Cerebellum 0.22 ± 0.050 0.16 ± 0.037 0.21 ± 0.018 ↵* P < 0.05 (R)-11C-KTP-Me vs. (RS)-11C-KTP-Me.
↵† P < 0.001 (S)-11C-KTP-Me vs. (RS)-11C-KTP-Me.
Absorbed doses of 11C-KTP-Me enantiomers were calculated using summed PET images from 5 to 45 min after tracer injection and are expressed as SUV. Data are expressed as mean ± SD ((R)-11C-KTP-Me, n = 3; others, n = 4).
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