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Basic Science Investigation |
1 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California; and 2 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California
Correspondence: For correspondence or reprints contact: Wolfgang A. Weber, MD, Nuclear Medicine, AR-264 CHS, UCLA School of Medicine, 10833 Le Conte Ave., Los Angeles, CA 90095-6942.E-mail: wweber{at}mednet.ucla.edu
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.
Key Words: 18F-FDG • microPET • SCID mice • study conditions • brown adipose tissue
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