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

Purpose 2-Deoxy-2-[F-18]fluoro-D-glucose ([F-18]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 [F-18] FDG levels, this study evaluated how these variables globally and regionally affect both [F-18] FDG uptake and kinetics in murine brain. Procedures Sixty-minute dynamic [F-18] FDG PET scans were performed in adult male C57BL/6 mice anesthetized with isoflurane [control (in 100 % O-2), in medical air, in 100 % O-2 + insulin pre-treatment, and in 100 % O-2 after 18 h 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. Results Ketamine/xylazine and chloral hydrate anesthesia induced a lower whole-brain uptake of [F-18] FDG (2.86 +/- 0.67 %ID/cc, p < 0.001; 4.25 +/- 0.28 %ID/cc, p = 0.0179, respectively) compared to isoflurane anesthesia (5.04 +/- 0.19 %ID/cc). In addition, protocols affected differently distribution of [F-18] FDG uptake in brain regions. Ketamine/xylazine reduced [F-18] FDG influx rate in murine brain (0.0135 +/- 0.0009 vs 0.0247 +/- 0.0014 ml/g/min; p < 0.005) and chloral hydrate increased MRGlu (66.72 +/- 3.75 vs 41.55 +/- 3.06 mu mol/min/100 ml; p < 0.01) compared to isoflurane. Insulin-pretreated animals showed a higher influx rate (0.0477 +/- 0.0101 ml/min/g; p < 0.05) but a reduced MRGlu (21.92 +/- 3.12 mu mol/min/100 ml; p < 0.01). Blood glucose levels were negatively correlated to [F-18] FDG uptake and influx rate, but positively correlated to MRGlu. Conclusions Choice of anesthesia and pre-conditioning affect not only [F-18] 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 [F-18] FDG studies due to its great influence on the uptake and distribution of the tracer along the brain regions.