TY - JOUR T1 - In Vivo Expression of Cyclooxygenase-1 in Activated Microglia and Macrophages During Neuroinflammation Visualized by PET with <sup>11</sup>C-Ketoprofen Methyl Ester JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1094 LP - 1101 DO - 10.2967/jnumed.110.084046 VL - 52 IS - 7 AU - Miho Shukuri AU - Misato Takashima-Hirano AU - Keiko Tokuda AU - Tadayuki Takashima AU - Kiyoshi Matsumura AU - Osamu Inoue AU - Hisashi Doi AU - Masaaki Suzuki AU - Yasuyoshi Watanabe AU - Hirotaka Onoe Y1 - 2011/07/01 UR - http://jnm.snmjournals.org/content/52/7/1094.abstract N2 - Cyclooxygenase (COX)-1 and -2 are prostanoid-synthesizing enzymes that play important roles in the regulation of neuroinflammation and in the development of neurodegenerative disorders. However, the specific functions of these isoforms are still unclear. We recently developed 11C-labeled ketoprofen methyl ester as a PET probe that targets the COXs for imaging neuroinflammation, though its responsible isoform is yet to be determined. In the present study, we performed ex vivo and in vivo imaging studies with 11C-ketoprofen methyl ester and determined the contributions of the COX isoforms during the neuroinflammatory process. Methods: To identify the COX isoform responsible for 11C-ketoprofen methyl ester in the brain, we examined the ex vivo autoradiography of 11C-ketoprofen methyl ester using COX-deficient mice. Time-dependent changes in accumulation of 11C-ketoprofen methyl ester during the neuroinflammatory process were evaluated by PET in rats with hemispheric neuroinflammation induced by intrastriatal injection of lipopolysaccharide or quinolinic acid. In both rat models, cell-type specificity of COX isoform expression during neuroinflammation was identified immunohistochemically. Results: Ex vivo autoradiographic analysis of COX-deficient mice revealed a significant reduction of 11C-ketoprofen methyl ester accumulation only in COX-1–deficient mice, not COX-2–deficient mice. PET of rats after intrastriatal injection of lipopolysaccharide showed a significant increase in accumulation of 11C-ketoprofen methyl ester in the inflamed area. This increase was evident at the early phase of 6 h, peaked at day 1, and then returned to basal levels by day 7. In addition, immunohistochemical analysis revealed that the population of activated microglia and macrophages was elevated at the early phase with COX-1 expression but not COX-2. A significant increase in 11C-ketoprofen methyl ester accumulation was also observed at day 1 after intrastriatal injection of quinolinic acid, with increased COX-1–expressing activated microglia and macrophages. Conclusion: We have identified 11C-ketoprofen methyl ester as a COX-1–selective PET probe, and using this, we have also demonstrated a time-dependent expression of COX-1 in activated microglia and macrophages during the neuroinflammatory process in the living brain. Thus, COX-1 may play a crucial role in the pathology of neuroinflammation and might be a critical target for the diagnosis and therapy of neurodegenerative disorders. ER -