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 (18)F-FDG uptake in murine tumor models, but the need for anesthesia raises concern over its potential influence on (18)F-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 micromol/L concentration of xylazine, ketamine, xylazine plus ketamine (Xy/Ke), or pentobarbital and were measured for (18)F-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 (18)F-FDG 15 min later. Biodistribution studies and plasma glucose and insulin assays were performed 45 min after injection. Separate anesthetized and control mice underwent (18)F-FDG PET.


RESULTS
(18)F-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 (18)F-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 (18)F-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.


CONCLUSIONS
Xy/Ke anesthesia markedly elevates blood (18)F-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 (18)F-FDG kinetics and PET images of tumor-bearing mice and should be considered when such studies are performed.
Lee
Kyung-Han
KH
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Ko
Bong-Ho
BH
Paik
Jin-Young
JY
Jung
Kyung-Ho
KH
Choe
Yearn Seong
YS
Choi
Yong
Y
Kim
Byung-Tae
BT
D000777:Anesthetics / Q000008:administration & dosage*; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D045744:Cell Line, Tumor; D004347:Drug Interactions; D005215:Fasting / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007328:Insulin / Q000097:blood*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000777:Anesthetics; D007328:Insulin; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18