11C-(R)-PK11195 PET Imaging of Microglial Activation and Response to Minocycline in Zymosan-Treated Rats

摘要: The ability to monitor white-matter inflammation in the central nervous system and detect changes after administration of antiinflammatory compounds is great importance several diseases, including multiple sclerosis (MS). We sought determine whether PET could increases binding 11C-(R)-PK11195 focal inflammatory lesions rat brain reduction this effect by minocycline treatment. Under normal physiologic conditions, microglia are distributed throughout a quiescent state (1). However, become activated response pathologic insult, primarily at site injury (2). prolonged release proinflammatory cytokines thought play critical role chronic long-term damage MS patients (3). Activation components innate immune system, such as microglia, mediated Toll-like receptors (1,4). injection zymosan, cell wall preparation from Saccharomyces cerevisiae that acts receptor-2 agonist, into white matter has been found activate resident produce resemble certain aspects those (5–7). Minocycline second-generation tetracycline displays antibiotic activity across wide range bacterial types also possesses (8). Mino-cycline being tested clinical trials thus far shown promise potential treatment (9–12). In contrast most immunosuppressive treatments available for patients, which predominantly target adaptive exhibits direct effects on (13,14). The isoquinoline PK11195 binds translocator protein (18 kDa), whose expression be enhanced during activation (2,15–17). radiolabeled isomer imaged with humans, whom its uptake correlated MRI measures postmortem histology (15,18–21). used microglial rodent models human disease involving neuroinflammation (22–25). This study was designed establish model corpus callosum led increased measured systemic compound would reduce effect.