Department of Diagnostic Radiology, School of Medicine, University of Louisville, Louisville, KY, USA; Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
Transl Oncol. 2014 Apr;7(2):240-7. doi: 10.1016/j.tranon.2014.02.010. Epub 2014 Mar 4.
This study revisited (18)F-fluorodeoxyglucose ((18)F-FDG) uptake and its relationship to hypoxia in various tumor models.
We generated peritoneal carcinomatosis and subcutaneous xenografts of colorectal cancer HT29, breast cancer MDA-MB-231, and non-small cell lung cancer A549 cell lines in nude mice. The partial oxygen pressure (pO2) of ascites fluid was measured. (18)F-FDG accumulation detected by digital autoradiography was related to tumor hypoxia visualized by pimonidazole binding and glucose transporter-1 (GLUT-1) in frozen tumor sections.
Ascites pO2 was 0.90 ± 0.53 mm Hg. Single cancer cells and clusters suspended in ascites fluid as well as submillimeter serosal tumors stained positive for pimonidazole and GLUT-1 and had high (18)F-FDG uptake. In contrast, (18)F-FDG uptake was significantly lower in normoxic portion (little pimonidazole binding or GLUT-1 expression) of larger serosal tumors or subcutaneous xenografts, which was not statistically different from that in the liver.
Glucose demand ((18)F-FDG uptake) in severely hypoxic ascites carcinomas and hypoxic portion of larger tumors is significantly higher than in normoxic cancer cells. Warburg effect originally obtained from Ehrlich ascites carcinoma may not apply to normoxic cancer cells. Our findings may benefit the better understanding of (18)F-FDG PET in oncology application.
本研究重新探讨了（18）F-氟脱氧葡萄糖（（18）F-FDG）摄取及其与各种肿瘤模型缺氧之间的关系。
我们在裸鼠中生成结直肠癌细胞 HT29、乳腺癌 MDA-MB-231 和非小细胞肺癌 A549 细胞系的腹膜癌病和皮下异种移植物。测量腹水的部分氧压（pO2）。通过数字放射自显影检测到的（18）F-FDG 积聚与冷冻肿瘤切片中通过吡莫硝唑结合和葡萄糖转运蛋白-1（GLUT-1）可视化的肿瘤缺氧相关。
腹水 pO2 为 0.90±0.53mmHg。悬浮在腹水中的单个癌细胞和细胞簇以及亚毫米级的浆膜肿瘤对吡莫硝唑和 GLUT-1 呈阳性染色，并且具有高（18）F-FDG 摄取。相比之下，较大浆膜肿瘤或皮下异种移植物的氧合部分（吡莫硝唑结合或 GLUT-1 表达较少）的（18）F-FDG 摄取明显较低，与肝脏无统计学差异。
严重缺氧的腹水中的癌细胞和较大肿瘤的缺氧部分的葡萄糖需求（（18）F-FDG 摄取）明显高于氧合癌细胞。最初从 Ehrlich 腹水癌中获得的Warburg 效应可能不适用于氧合癌细胞。我们的发现可能有助于更好地理解（18）F-FDG PET 在肿瘤学中的应用。
