Anesthesia and Preconditioning Induced Changes in Mouse Brain [18F] FDG Uptake and Kinetics

Abstract

Purpose2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) has been widely used for imaging brain metabolism. Tracer injection in anesthetized animals is a prerequisite for performing dynamic positron emission tomography (PET) scanning. Since preconditioning, as well as anesthesia, has been described to potentially influence brain [18F] FDG levels, this study evaluated how these variables globally and regionally affect both [18F] FDG uptake and kinetics in murine brain.ProceduresSixty-minute dynamic [18F] FDG PET scans were performed in adult male C57BL/6 mice anesthetized with isoflurane [control (in 100\xa0% O2), in medical air, in 100\xa0% O2\u2009+\u2009insulin pre-treatment, and in 100\xa0% O2 after 18\xa0h fasting], ketamine/xylazine, sevoflurane, and chloral hydrate. An additional group was scanned after awake uptake. Blood glucose levels were determined, and data was analyzed by comparing percent injected dose per cc tissue (%ID/cc) and glucose influx rate and metabolic rate (MRGlu) calculated by Patlak plot.ResultsKetamine/xylazine and chloral hydrate anesthesia induced a lower whole-brain uptake of [18F] FDG (2.86\u2009±\u20090.67\xa0%ID/cc, p\u2009<\u20090.001; 4.25\u2009±\u20090.28\xa0%ID/cc, p\u2009=\u20090.0179, respectively) compared to isoflurane anesthesia (5.04\u2009±\u20090.19\xa0%ID/cc). In addition, protocols affected differently distribution of [18F] FDG uptake in brain regions. Ketamine/xylazine reduced [18F] FDG influx rate in murine brain (0.0135\u2009±\u20090.0009 vs 0.0247\u2009±\u20090.0014\xa0ml/g/min; p\u2009<\u20090.005) and chloral hydrate increased MRGlu (66.72\u2009±\u20093.75 vs 41.55\u2009±\u20093.06\xa0μmol/min/100\xa0ml; p\u2009<\u20090.01) compared to isoflurane. Insulin-pretreated animals showed a higher influx rate (0.0477\u2009±\u20090.0101\xa0ml/min/g; p\u2009<\u20090.05) but a reduced MRGlu (21.92\u2009±\u20093.12\xa0μmol/min/100\xa0ml; p\u2009<\u20090.01). Blood glucose levels were negatively correlated to [18F] FDG uptake and influx rate, but positively correlated to MRGlu.ConclusionsChoice of anesthesia and pre-conditioning affect not only [18F] FDG uptake but also kinetics and regional distribution in the mouse brain. Both anesthesia and pre-conditioning should be carefully considered in the interpretation of [18F] FDG studies due to its great influence on the uptake and distribution of the tracer along the brain regions.