%0 Journal Article
%T MicroPET/CT Imaging of [18F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity
%A Xuan Zhang
%A Merle G. Paule
%A Glenn D. Newport
%A Fang Liu
%A Ralph Callicott
%A Shuliang Liu
%A Marc S. Berridge
%A Scott M. Apana
%A William Slikker Jr.
%A Cheng Wang
%J ISRN Anesthesiology
%D 2012
%R 10.5402/2012/261640
%X Background. The inhalation anesthetics nitrous oxide (N2O) and isoflurane (ISO) are used in surgical procedures for human infants. Injury to the central nervous system is often accompanied by localization of activated microglia or astrocytosis at the site of injury. The tracer that targets to the peripheral benzodiazepine receptor (PBR), [18F]N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]-FEPPA), has been reported as a sensitive biomarker for the detection of neuronal damage/inflammation. Methods. On postnatal day (PND) 5 or 6 rhesus monkey neonates were exposed to a mixture of N2O/oxygen and ISO for 8 hours and control monkeys were exposed to room air. MicroPET/CT images with [18F]-FEPPA were obtained for each monkey 1 day, one week, three weeks, and 6 months after the anesthetic exposure. Results. The radiotracer quickly distributed into the brains of both treated and control monkeys on all scan days. One day after anesthetic exposure, the uptake of [18F]-FEPPA was significantly increased in the temporal lobe. One week after exposure, the uptake of [18F]-FEPPA in the frontal lobe of treated animals was significantly greater than that in controls. Conclusions. These findings suggest that microPET imaging is capable of dynamic detection of inhaled anesthetic-induced brain damage in different brain regions of the nonhuman primate. 1. Introduction General anesthetics bring about a reversible loss of consciousness by regulating neuronal excitability. The mechanisms underlying this action include suppression of excitatory NMDA receptor-mediated transmission and/or potentiation of inhibitory GABAA receptor currents in the central nervous system [1¨C3]. Nitrous oxide (N2O), a gaseous inhalation anesthetic agent, is often given in combination with more powerful volatile anesthetics such as isoflurane (ISO) to maintain general anesthesia in pregnant women, neonates and infants requiring surgery and/or other invasive or painful procedures. Experimental findings both in vitro and in vivo suggest that general anesthetics can induce neurotoxicity during the period of rapid neuronal growth and synaptogenesis (the brain growth spurt period) in the developing animal brain [1, 4¨C6]. Because of the similarity of the physiology, pharmacology, metabolism, reproductive systems, and developmental trajectory and time course of the nonhuman primate to that of the human, they are exceptionally good animal models of neurodevelopment and for the detection of potential neurodegenerative effects associated with exposure to inhaled anesthetics. In a parallel
%U http://www.hindawi.com/journals/isrn.anesthesiology/2012/261640/