RT Journal Article SR Electronic T1 Impact of Animal Handling on the Results of 18F-FDG PET Studies in Mice JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 999 OP 1006 VO 47 IS 6 A1 Fueger, Barbara J. A1 Czernin, Johannes A1 Hildebrandt, Isabel A1 Tran, Chris A1 Halpern, Benjamin S. A1 Stout, David A1 Phelps, Michael E. A1 Weber, Wolfgang A. YR 2006 UL http://jnm.snmjournals.org/content/47/6/999.abstract AB Small-animal PET scanning with 18F-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 18F-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 18F-FDG PET and to develop an imaging protocol that optimizes visualization of tumor xenografts. Methods: Groups of severe combined immunodeficient (SCID) mice were first imaged by microPET with free access to food, at room temperature (20°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°C), and (c) general anesthesia using isoflurane or ketamine/xylazine on the 18F-FDG biodistribution was evaluated. Subcutaneously implanted human A431 epidermoid carcinoma and U251 glioblastoma cells served as tumor models. Results: Depending on the study conditions, 18F-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 18F-FDG uptake by brown adipose tissue observed under the reference condition and markedly improved visualization of tumor xenografts. Although tumor 18F-FDG uptake was not above background activity under the reference condition, tumors demonstrated marked focal 18F-FDG uptake in warmed and fasted animals. Quantitatively, tumor 18F-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 18F-FDG uptake. Isoflurane markedly reduced 18F-FDG uptake by brown adipose tissue and skeletal muscle but increased the activity concentration in liver, myocardium, and kidney. Conclusion: Animal handling has a dramatic effect on 18F-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 18F-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.