Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Mol Imaging. 2013 Jan-Feb;12(1):49-58.
Tumor hypoxia and tumor metabolism are linked through the activation of metabolic genes following hypoxia-inducible factor 1 (HIF-1) activation. This raises the question of whether this relationship can be exploited to improve 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography ([(18)F]FDG-PET). To do this, [(18)F]FDG uptake was investigated after chemical induction of hypoxia and chemical activation of HIF-1 in an in vitro and an in vivo model of a human colorectal carcinoma. [(18)F]FDG uptake, HIF-1α protein levels, and messenger ribonucleic acid expression of glucose transporter 1 (GLUT1), hexokinase 2, HIF-1α, and carbonic anhydrase IX (CA IX) were determined in HT29 cells after treatment with 200 μM CoCl(2) and 500 μM dimethyloxalylglycine (DMOG). In an HT29 xenograft, the distribution of endogenous and exogenous markers of hypoxia was investigated using immunohistochemistry, and tumor [(18)F]FDG uptake was determined after treatment with a single dose of 5 mg/kg hydralazine and 8 mg DMOG. Treatment of HT29 cells with CoCl(2) and DMOG induced functional HIF-1 and resulted in increased [(18)F]FDG uptake. In an HT29 xenograft, a similar spatial distribution of pimonidazole, CA IX, and GLUT1 was found, and treatment with DMOG resulted in significant increases in maximum and mean standardized uptake values using [(18)F]FDG-PET. Chemical activation of HIF-1 can increase in vitro and in vivo [(18)F]FDG uptake. Imaging after pharmacologic HIF-1 activation might increase tumor [(18)F]FDG uptake when using [(18)F]FDG-PET.
肿瘤缺氧和肿瘤代谢通过缺氧诱导因子 1（HIF-1）激活后代谢基因的激活而联系在一起。这就提出了一个问题，即这种关系是否可以被利用来改善 2-脱氧-2-[(18)F]氟-D-葡萄糖正电子发射断层扫描([(18)F]FDG-PET)。为此，在人结直肠癌的体外和体内模型中，研究了在化学诱导缺氧和化学激活 HIF-1 后[（18）F]FDG 的摄取。在用 200μM CoCl2 和 500μM 二甲草酰甘氨酸（DMOG）处理 HT29 细胞后，测定了[（18）F]FDG 摄取、HIF-1α 蛋白水平以及葡萄糖转运蛋白 1（GLUT1）、己糖激酶 2、HIF-1α 和碳酸酐酶 9（CAIX）的信使核糖核酸表达。在 HT29 异种移植物中，使用免疫组织化学研究了内源性和外源性缺氧标志物的分布，并用单剂量 5mg/kg 肼屈嗪和 8mg DMOG 处理后测定了肿瘤[（18）F]FDG 摄取。用 CoCl2 和 DMOG 处理 HT29 细胞诱导功能性 HIF-1，并导致[（18）F]FDG 摄取增加。在 HT29 异种移植物中，发现了 pimonidazole、CAIX 和 GLUT1 的相似空间分布，并用 DMOG 处理导致使用[（18）F]FDG-PET 的最大和平均标准化摄取值显著增加。HIF-1 的化学激活可以增加体外和体内[（18）F]FDG 摄取。在用[（18）F]FDG-PET 时，药物 HIF-1 激活后的成像可能会增加肿瘤[（18）F]FDG 摄取。
