PT  - JOURNAL ARTICLE
AU  - Zhang, Guojian
AU  - Li, Jianbo
AU  - Wang, Xuemei
AU  - Li, Xiao-Feng
TI  - <sup>18</sup>F-FDG uptake in non-small cell lung cancer: Warburg effect, reverse Warburg effect or Pasteur effect?
DP  - 2015 May 01
TA  - Journal of Nuclear Medicine
PG  - 503--503
VI  - 56
IP  - supplement 3
4099  - http://jnm.snmjournals.org/content/56/supplement_3/503.short
4100  - http://jnm.snmjournals.org/content/56/supplement_3/503.full
SO  - J Nucl Med2015 May 01; 56
AB  - 503 Objectives To observe the role of Warburg effect, reverse Warburg effect or Pasteur effect on 18F-FDG uptake in cancerMethods In in vivo studies, 18F-FDG micro-PET scans were performed in 5 mice bearing NSCLC 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.Results Micro-PET scans were performed in fed animals on day 1 and after overnight fasting. 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, change in spatial intratumoral distribution of 18F-FDG was remarkably different in all mice. Tumor 18F-FDG SUVmean and SUVmax were not significantly different between fed and fasted animals. In ex vivo studies, in fasted mice, there was spatial co-localization between high levels of 18F-FDG uptake and pimonidazole binding hypoxic cancer cells, pimonidazole-negative normoxic cancer cells and noncancerous stroma was 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.Conclusions 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, i.e. "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.Research Support Kentucky Lung Cancer Research program award (cycle 9), Inner Mongolia Natural Science Foundation awards (2012MS1153, 2014MS0835 and 2014MS0859) and National Natural Science Foundation of China award (81360227).