Impact of animal handling on the results of 18F-FDG PET studies in mice

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Journal of Nuclear Medicine (Impact Factor: 6.16). 07/2006; 47(6):999-1006.
Source: PubMed


Small-animal PET scanning with (18)F-FDG is increasingly used in murine models of human diseases. However, the impact of dietary conditions, mode of anesthesia, and ambient temperature on the biodistribution of (18)F-FDG in mice has not been systematically studied so far. The aim of this study was to determine how these factors affect assessment of tumor glucose use by (18)F-FDG PET and to develop an imaging protocol that optimizes visualization of tumor xenografts.
Groups of severe combined immunodeficient (SCID) mice were first imaged by microPET with free access to food, at room temperature (20 degrees C), and no anesthesia during the uptake period (reference condition). Subsequently, the impact of (a) fasting for 8-12 h, (b) warming the animals with a heating pad (30 degrees C), and (c) general anesthesia using isoflurane or ketamine/xylazine on the (18)F-FDG biodistribution was evaluated. Subcutaneously implanted human A431 epidermoid carcinoma and U251 glioblastoma cells served as tumor models.
Depending on the study conditions, (18)F-FDG uptake by normal tissues varied 3-fold for skeletal muscle, 13-fold for brown adipose tissue, and 15-fold for myocardium. Warming and fasting significantly reduced the intense (18)F-FDG uptake by brown adipose tissue observed under the reference condition and markedly improved visualization of tumor xenografts. Although tumor (18)F-FDG uptake was not above background activity under the reference condition, tumors demonstrated marked focal (18)F-FDG uptake in warmed and fasted animals. Quantitatively, tumor (18)F-FDG uptake increased 4-fold and tumor-to-organ ratios were increased up to 17-fold. Ketamine/xylazine anesthesia caused marked hyperglycemia and was not further evaluated. Isoflurane anesthesia only mildly increased blood glucose levels and had no significant effect on tumor (18)F-FDG uptake. Isoflurane markedly reduced (18)F-FDG uptake by brown adipose tissue and skeletal muscle but increased the activity concentration in liver, myocardium, and kidney.
Animal handling has a dramatic effect on (18)F-FDG biodistribution and significantly influences the results of microPET studies in tumor-bearing mice. To improve tumor visualization mice should be fasted and warmed before (18)F-FDG injection and during the uptake period. Isoflurane appears well suited for anesthesia of tumor-bearing mice, whereas ketamine/xylazine should be used with caution, as it may induce marked hyperglycemia.

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Available from: Barbara Füger, Jul 09, 2014
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    • "This uptake period (time between radiotracer injection and image acquisition initiation) was kept consistent for all mice to ensure that the radiotracer distribution was at similar point of the plateau in [ 18 F]-FDG pharmacokinetics, where tumor uptake was slowly rising and background tissue uptake was slowly decreasing. Mouse preparation protocol factors such as anesthesia, external warming, and restricted diets or fasting affect intersubject variation in [ 18 F]-FDG metabolism and biodistribution in mice [17]. Therefore, the mice were placed in clean cages and fed a high-fat, low-protein, and low-carbohydrate ketogenic diet with free access to water for 12 to 16 hours before the [ 18 F]-FDG-PET/CT. "
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    • "On the other hand, one night on a low-carbohydrate, high-fat diet seems sufficient to ensure good myocardial suppression [9]. Despite efforts to standardize patient preparation before PET studies, myocardial uptake of 18F-FDG has proven highly variable in both clinical and preclinical applications owing to individual patient characteristics [10], [11] or to differences in animal handling [12], [13]. "
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    • "Mice were fasted for 6 hours and were subsequently anesthetized using isoflurane/compressed air before 18F-FDG injection until the end of the experiment. Before and during scans, body temperature was kept within normal range using heated pads and heating lamps [26]. At 45 minutes before imaging, mice were injected intravenously (i.v.) through a tail vein catheter with 0.2 mL/10.2 "
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