The radiation response of cells from 9L gliosarcoma tumours is correlated with [F18]-EF5 uptake.
The radiation response of cells from 9L gliosarcoma tumours is correlated with [F18]-EF5 uptake.
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DOI：
10.3109/09553000903242172
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发表时间：
2009-12
影响因子：
2.6
通讯作者：
Evans SM
中科院分区：
文献类型：
--
作者：
Koch CJ;Shuman AL;Jenkins WT;Kachur AV;Karp JS;Freifelder R;Dolbier WR Jr;Evans SM
肿瘤缺氧影响动物和人类的癌症生物学和治疗抗性。本研究的目的是确定EF 5（[2-（2-硝基-1-H-咪唑-1-基）-N-（2，2，3，3，3-五氟丙基）-乙酰胺]）结合和/或放射性药物摄取是否与9 L胶质肉瘤肿瘤中的单剂量辐射反应相关。22个9 L肿瘤在雄性Fischer大鼠中生长。给大鼠施用低比活度18F-EF 5，照射它们的肿瘤并评估细胞存活和缺氧。缺氧试验包括EF 5结合抗体对结合药物加合物和γ计数的18F-EF 5肿瘤摄取与正常肌肉和血液摄取相比。将这些试验与细胞辐射反应（体内至体外试验）进行比较。在六个病例中，还使用PET（正电子发射断层扫描）相机（PENN G-PET）的图像分析了肿瘤与肌肉的吸收。9 L肿瘤细胞的辐射反应的肿瘤间变化与18F标记的EF 5的摄取显著相关（即，包括结合的和未结合的药物），使用肿瘤与肌肉或肿瘤与血液γ计数比率。在进行成像的肿瘤中，图像分析和伽马计数分析之间存在显著相关性。相同的22个肿瘤的细胞辐射响应的肿瘤间变化也与由于EF 5结合的平均流式细胞术信号相关。据我们所知，这是第一个动物模型/药物组合证明了放射反应的相关性，从个别肿瘤与药物代谢的肿瘤细胞使用免疫组织化学或非侵入性技术。
Tumour hypoxia affects cancer biology and therapy-resistance in both animals and humans. The purpose of this study was to determine whether EF5 ([2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide]) binding and/or radioactive drug uptake correlated with single-dose radiation response in 9L gliosarcoma tumours. Twenty-two 9L tumours were grown in male Fischer rats. Rats were administered low specific activity 18F-EF5 and their tumours irradiated and assessed for cell survival and hypoxia. Hypoxia assays included EF5 binding measured by antibodies against bound-drug adducts and gamma counts of 18F-EF5 tumour uptake compared with uptake by normal muscle and blood. These assays were compared with cellular radiation response (in vivo to in vitro assay). In six cases, uptake of tumour versus muscle was also assayed using images from a PET (positron emission tomography) camera (PENN G-PET). The intertumoural variation in radiation response of 9L tumour-cells was significantly correlated with uptake of 18F-labelled EF5 (i.e., including both bound and non-bound drug) using either tumour to muscle or tumour to blood gamma count ratios. In the tumours where imaging was performed, there was a significant correlation between the image analysis and gamma count analysis. Intertumoural variation in cellular radiation response of the same 22 tumours was also correlated with mean flow cytometry signal due to EF5 binding. To our knowledge, this is the first animal model/drug combination demonstrating a correlation of radioresponse for tumour-cells from individual tumours with drug metabolism using either immunohistochemical or non-invasive techniques.
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影响因子：
3.1
作者：
Bergman, J;Solin, O
通讯作者：
Solin, O
DOI：
10.1007/s00259-003-1404-x
发表时间：
2004-04-01
影响因子：
9.1
作者：
Grönroos, T;Bentzen, L;Solin, O
通讯作者：
Solin, O
DOI：
10.1016/s0360-3016(00)01494-2
发表时间：
2001-02-01
影响因子：
7
作者：
Evans, SM;Hahn, SM;Koch, CJ
通讯作者：
Koch, CJ
DOI：
10.1016/s0360-3016(99)00104-2
发表时间：
1999-07-15
影响因子：
7
作者：
Kavanagh, MC;Tsang, V;Hill, RP
通讯作者：
Hill, RP
影响因子：
5.7
作者：
HOCKEL, M;KNOOP, C;VAUPEL, P
通讯作者：
VAUPEL, P