PT - JOURNAL ARTICLE AU - Guojian Zhang AU - Jianbo Li AU - Xuemei Wang AU - Yuanyuan Ma AU - Xindao Yin AU - Feng Wang AU - Huaiyu Zheng AU - Xiaoxian Duan AU - Gregory C. Postel AU - Xiao-Feng Li TI - The Reverse Warburg Effect and <sup>18</sup>F-FDG Uptake in Non–Small Cell Lung Cancer A549 in Mice: A Pilot Study AID - 10.2967/jnumed.114.148254 DP - 2015 Apr 01 TA - Journal of Nuclear Medicine PG - 607--612 VI - 56 IP - 4 4099 - http://jnm.snmjournals.org/content/56/4/607.short 4100 - http://jnm.snmjournals.org/content/56/4/607.full SO - J Nucl Med2015 Apr 01; 56 AB - The purpose of this study was to observe the effect of fasting and feeding on 18F-FDG uptake in a mouse model of human non–small cell lung cancer. Methods: In in vivo studies, 18F-FDG small-animal PET scans were acquired in 5 mice bearing non–small cell lung cancer A549 xenografts on each flank with continuous feeding and after overnight fasting to observe the changes in intratumoral distribution of 18F-FDG and tumor 18F-FDG standardized uptake value (SUV). In ex vivo studies, intratumoral spatial 18F-FDG distribution assessed by autoradiography was compared with the tumor microenvironment (including hypoxia by pimonidazole and stroma by hematoxylin and eosin stain). Five overnight-fasted mice and 5 fed mice with A549 tumors were observed. Results: Small-animal PET scans were obtained in fed animals on day 1 and in the same animals after overnight fasting; the lapse was approximately 14 h. Blood glucose concentration after overnight fasting was not different from fed mice (P = 0.42), but body weight loss was significant after overnight fasting (P = 0.001). Intratumoral distribution of 18F-FDG was highly heterogeneous in all tumors examined, and change in spatial intratumoral distribution of 18F-FDG between 2 sets of PET images from the same mouse was remarkably different in all mice. Tumor 18F-FDG mean SUV and maximum SUV were not significantly different between fed and fasted animals (all P &gt; 0.05, n = 10). Only tumor mean SUV weakly correlated with blood glucose concentration (R2 = 0.17, P = 0.03). In ex vivo studies, in fasted mice, there was spatial colocalization between high levels of 18F-FDG uptake and pimonidazole-binding hypoxic cancer cells; in contrast, pimonidazole-negative normoxic cancer cells and noncancerous stroma were associated with low 18F-FDG uptake. However, high 18F-FDG uptake was frequently observed in noncancerous stroma of tumors but rarely in viable cancer cells of the tumors in fed animals. Conclusion: Host dietary status may play a key role in intratumoral distribution of 18F-FDG. In the fed animals, 18F-FDG accumulated predominantly in noncancerous stroma in the tumors, that is, reverse Warburg effect. In contrast, in fasted status, 18F-FDG uptake was found in hypoxic cancer cells component (Pasteur effect). Our findings may provide a better understanding of competing cancer glucose metabolism hypotheses: the Warburg effect, reverse Warburg effect, and Pasteur effect.