Biological characteristics of intratumoral [F-18]‑fluoromisonidazole distribution in a rodent model of glioma.
Biological characteristics of intratumoral [F-18]‑fluoromisonidazole distribution in a rodent model of glioma.
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DOI：
10.3892/ijo.2013.1781
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发表时间：
2013-03
影响因子：
5.2
通讯作者：
Kuge Y
中科院分区：
文献类型：
--
作者：
Hatano T;Zhao S;Zhao Y;Nishijima K;Kuno N;Hanzawa H;Sakamoto T;Tamaki N;Kuge Y
精确成像以识别肿瘤中的缺氧区域是放射治疗计划的关键。[F-18]-氟咪唑（[F-18]-FMISO）广泛用于肿瘤缺氧成像，并有可能优化放射治疗计划。然而，肿瘤内[F-18]-FMISO分布的生物学特征尚未得到充分研究。在低氧细胞中，诱导细胞增殖的低氧诱导因子-1（HIF-1）靶蛋白、诱导细胞增殖和葡萄糖代谢的HIF-1靶蛋白、葡萄糖转运蛋白-1（Glut-1）和己糖激酶-II（HK-II）被上调。在这项研究中，我们通过放射自显影（ARG）确定了[F-18]-FMISO的肿瘤内分布，并将其与胶质瘤大鼠模型中的哌莫硝唑摄取、Glut-1表达、肿瘤增殖活性（Ki-67指数）和葡萄糖代谢（[C-14]2-氟-2-脱氧-D-葡萄糖摄取; [C-14]-FDG）进行了比较。5只C6胶质瘤大鼠注射[F-18]-FMISO和[C-14]-FDG。90 min后注射哌莫硝唑，60 min后处死大鼠，取肿瘤组织切片。相邻切片用于匹莫硝唑、Glut-1和Ki-67的ARG和免疫组织化学（IHC）分析。[F-18]-FMISO ARG图像分为高[F-18]-FMISO摄取（FMISO+）和低[F-18]-FMISO摄取（FMISO−）区域。在FMISO+和FMISO-上的感兴趣区域（ROI）中评价了Pimonidazole和Glut-1表达水平、Ki-67指数和[C-14]-FDG分布。[F-18]-FMISO分布与哌莫硝唑分布基本一致。FMISO+组Glut-1阳性染色面积百分比（阳性%）显著高于FMISO组（FMISO+组24±8%，FMISO-组9±4%; P<0.05）。FMISO+和FMISO-之间的Ki-67指数和[C-14]-FDG摄取无显著差异（对于Ki-67，FMISO+为10±5%，FMISO-为12±5%，P = ns;对于[C-14]-FDG，FMISO+为1.4±0.3% ID/g/kg，FMISO-为1.3±0.3% ID/g/kg，P = ns）。肿瘤内[F-18]-FMISO分布反映了肿瘤缺氧和缺氧相关基因产物Glut-1的表达;然而，它并不反映肿瘤增殖或葡萄糖代谢。我们的研究结果有助于阐明与放射治疗计划相关的肿瘤内[F-18]-FMISO分布的生物学特征。
Accurate imaging to identify hypoxic regions in tumors is key for radiotherapy planning. [F-18]-fluoromisonidazole ([F-18]-FMISO) is widely used for tumor hypoxia imaging and has the potential to optimize radio-therapy planning. However, the biological characteristics of intratumoral [F-18]-FMISO distribution have not yet been fully investigated. In hypoxic cells, the hypoxia-inducible factor-1 (HIF-1) target proteins that induce cellular prolif-HIF-1) target proteins that induce cellular proliferation and glucose metabolism, glucose transporter-1 (Glut-1) and hexokinase-II (HK-II), are upregulated. In this study, we determined the intratumoral distribution of [F-18]-FMISO by autoradiography (ARG) and compared it with pimonidazole uptake, expression of Glut-1, tumor proliferative activity (Ki-67 index) and glucose metabolism ([C-14]2-fluoro-2-deoxy-D-glucose uptake; [C-14]-FDG) in a glioma rat model. Five C6 glioma-bearing rats were injected with [F-18]-FMISO and [C-14]-FDG. After 90 min, the rats were injected with pimonidazole and 60 min later, the rats were sacrificed and tumor tissues were sectioned into slices. The adjacent slices were used for ARG and immunohistochemical (IHC) analyses of pimonidazole, Glut-1 and Ki-67. [F-18]-FMISO ARG images were divided into regions of high [F-18]-FMISO uptake (FMISO+) and low [F-18]-FMISO uptake (FMISO−). Pimonidazole and Glut-1 expression levels, Ki-67 index and [C-14]-FDG distribution were evaluated in the regions of interest (ROIs) placed on FMISO+ and FMISO−. [F-18]-FMISO distribution was generally consistent with pimonidazole distribution. The percentage of positively stained areas (% positive) of Glut-1 in FMISO+ was significantly higher compared to FMISO (24±8% in FMISO+ and 9±4% in FMISO−; P<0.05). There were no significant differences in Ki-67 index and [C-14]-FDG uptake between FMISO+ and FMISO− (for Ki-67, 10±5% in FMISO+ and 12±5% in FMISO−, P = ns; for [C-14]-FDG, 1.4±0.3% ID/g/kg in FMISO+ and 1.3±0.3% ID/g/kg in FMISO−, P = ns). Intratumoral [F-18]-FMISO distribution reflected tumor hypoxia and expression of the hypoxia-related gene product Glut-1; it did not, however, reflect tumor proliferation or glucose metabolism. Our findings help elucidate the biological characteristics of intratumoral [F-18]-FMISO distribution that are relevant to radiotherapy planning.
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影响因子：
3.1
作者：
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