Anesthesia and Preconditioning Induced Changes in Mouse Brain [18F] FDG Uptake and Kinetics
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2-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.
Sixty-minute dynamic [18F] FDG PET scans were performed in adult male C57BL/6 mice anesthetized with isoflurane [control (in 100 % O2), in medical air, in 100 % O2 + insulin pre-treatment, and in 100 % O2 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.
Ketamine/xylazine and chloral hydrate anesthesia induced a lower whole-brain uptake of [18F] 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 [18F] FDG uptake in brain regions. Ketamine/xylazine reduced [18F] 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 μmol/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 μmol/min/100 ml; p < 0.01). Blood glucose levels were negatively correlated to [18F] FDG uptake and influx rate, but positively correlated to MRGlu.
Choice 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.
Key wordsIsoflurane Ketamine Sevoflurane Chloral hydrate Glucose
The authors thank A. Kanwischer, S. Eilert, and P. Felsch for skillful assistance.
This study was partially supported by the German Research Foundation (DFG, Clinical Research Group KFO311 and grant-in-aid TH2161/1-1).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest
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