Effects of anesthetic agents and fasting duration on ¹⁸F-FDG biodistribution and insulin levels in tumor-bearing mice

Small-animal PET has opened the way for imaging ¹⁸F-FDG uptake in murine tumor models, but the need for anesthesia raises concern over its potential influence on ¹⁸F-FDG kinetics. We thus investigated such effects on cultured cells and on tumor-bearing mice after short- and long-term fasting. Methods: Lewis lung carcinoma (LLC) cells and cardiomyoblasts were treated for 2 h with a 100 μmol/L concentration of xylazine, ketamine, xylazine plus ketamine (Xy/Ke), or pentobarbital and were measured for ¹⁸F-FDG uptake. LLC tumor-bearing C57BL6 mice that had been kept fasting for either 4 or 20 h were injected with Xy/Ke, pentobarbital, or saline and were administered 1.8 MBq of ¹⁸F-FDG 15 min later. Biodistribution studies and plasma glucose and insulin assays were performed 45 min after injection. Separate anesthetized and control mice underwent ¹⁸F-FDG PET. Results: ¹⁸F-FDG uptake in LLC cells was unaffected by anesthetic agents, whereas xylazine and ketamine caused a small increase of uptake in cardiomyoblasts. In mice kept fasting 4 h, Xy/Ke induced a marked elevation of ¹⁸F-FDG activity (percentage injected dose [%ID]) in blood (6.8 ± 0.9 %ID/g vs. 1.1 ± 0.6 %ID/g) and kidneys while decreasing myocardial uptake (2.3 ± 1.3 %ID/g vs. 4.7 ± 1.8 %ID/g). Target-to-blood ratios were significantly reduced. Pentobarbital caused a moderate increase in blood activity (2.5 ± 0.8 %ID/g), decreased myocardial uptake (2.8 ± 0.5 %ID/g), and reduced target-to-blood ratios. PET images of mice kept fasting 4 h were consistent with the biodistribution data. Insulin levels were lower with Xy/Ke and higher with pentobarbital. In mice kept fasting 20 h, Xy/Ke and pentobarbital increased blood ¹⁸F-FDG activity (5.5 ± 2.2 and 4.9 ± 0.9 %ID/g vs. 2.4 ± 0.3 %ID/g) and reduced target-to-blood ratios, but these changes were substantially attenuated, compared with those in mice kept fasting 4 h. In addition, insulin levels were low and unaffected by anesthesia. Conclusion: Xy/Ke anesthesia markedly elevates blood ¹⁸F-FDG activity and reduces tumor uptake ratios through inhibition of insulin release in mice kept fasting 4 h, whereas pentobarbital induces a similar but less severe response through insulin resistance. These metabolic effects, however, are substantially attenuated after 20 h of fasting. Hence both the choice of anesthetic and the duration of fasting have important effects on ¹⁸F-FDG kinetics and PET images of tumor-bearing mice and should be considered when such studies are performed.