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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Fueger
Barbara J
BJ
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Czernin
Johannes
J
Hildebrandt
Isabel
I
Tran
Chris
C
Halpern
Benjamin S
BS
Stout
David
D
Phelps
Michael E
ME
Weber
Wolfgang A
WA
D000822:Animal Husbandry / Q000379:methods*; D000818:Animals; D016477:Artifacts; D001522:Behavior, Animal / Q000502:physiology*; D004777:Environment; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009043:Motor Activity / Q000502:physiology*; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods / Q000662:veterinary*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D051598:Whole Body Imaging / Q000379:methods / Q000662:veterinary
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18