High 18F-FDG uptake in microscopic peritoneal tumors requires physiologic hypoxia.
High 18F-FDG uptake in microscopic peritoneal tumors requires physiologic hypoxia.
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DOI：
10.2967/jnumed.109.071233
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发表时间：
2010-04
期刊：
影响因子：
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通讯作者：
O'Donoghue JA
中科院分区：
文献类型：
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作者：
Li XF;Ma Y;Sun X;Humm JL;Ling CC;O'Donoghue JA
本研究的目的是检查18 F-氟脱氧葡萄糖（18 F-FDG）的摄取在裸鼠腹腔内生长的显微肿瘤，并将其与生理缺氧和葡萄糖转运蛋白-1（GLUT-1）的表达。将人结肠癌HT 29和HCT-8细胞腹腔内注射到裸鼠中以产生不同大小的播散性肿瘤。在禁食过夜后，在处死前1小时，对呼吸空气或碳源（95%O2 + 5%CO2）的动物静脉内施用18F-FDG以及缺氧标记物哌莫硝唑（PIMO）和细胞增殖标记物溴脱氧尿苷（BrdUrd）。Hoechst 33342是一种灌注标记物，在处死前1分钟给药。处死后，通过冷冻组织切片的数字放射自显影术评估18F-FDG的肿瘤内分布。将其与通过免疫荧光显微镜观察到的PIMO、GLUT-1表达、BrdUrd和Hoechst 33342的分布进行比较。小肿瘤（直径< 1 mm）具有高18 F-FDG蓄积，严重缺氧，GLUT-1表达高。较大的肿瘤（直径1-4 mm）通常具有低18 F-FDG蓄积，并且没有显著缺氧，GLUT 1表达较低。碳源呼吸显着降低18F-FDG的积累和肿瘤缺氧显微镜下肿瘤，但GLUT 1的表达几乎没有影响。在显微镜下肿瘤中有高的18F-FDG摄取，这与生理性缺氧和高GLUT-1表达在空间上相关。这种增强的摄取被carbogen呼吸消除，表明在没有生理缺氧的情况下，高GLUT 1表达本身不足以确保高18F-FDG摄取。
The objective of this study was to examine 18F-fluorodeoxyglucose (18F-FDG) uptake in microscopic tumors grown intraperitoneally in nude mice and to relate this to physiological hypoxia and glucose transporter-1 (GLUT-1) expression. Human colon cancer HT29 and HCT-8 cells were injected intraperitoneally into nude mice to generate disseminated tumors of varying sizes. Following overnight fasting, animals, either breathing air or carbogen (95% O2+ 5% CO2), were intravenously administered 18F-FDG together with the hypoxia marker pimonidazole (PIMO) and the cellular proliferation marker bromodeoxyuridine (BrdUrd) one hour before sacrifice. Hoechst 33342, a perfusion marker, was administered one minute before sacrifice. Following sacrifice, the intratumoral distribution of 18F-FDG was assessed by digital autoradiography of frozen tissue sections. This was compared with the distributions of PIMO, GLUT-1 expression, BrdUrd and Hoechst 33342 as visualized by immunofluorescent microscopy. Small tumors (< 1 mm diameter) had high 18F-FDG accumulation and were severely hypoxic with high GLUT-1 expression. Larger tumors (1–4 mm diameter) generally had low 18F-FDG accumulation and were not significantly hypoxic with low GLUT1 expression. Carbogen breathing significantly decreased 18F-FDG accumulation and tumor hypoxia in microscopic tumors but had little effect on GLUT1 expression. There was high 18F-FDG uptake in microscopic tumors which was spatially associated with physiological hypoxia and high GLUT-1 expression. This enhanced uptake was abrogated by carbogen breathing, indicating that in the absence of physiological hypoxia, high GLUT1 expression, by itself, was insufficient to ensure high 18F-FDG uptake.