Validating bladder cancer xenograft bioluminescence with magnetic resonance imaging: the significance of hypoxia and necrosis
Validating bladder cancer xenograft bioluminescence with magnetic resonance imaging: the significance of hypoxia and necrosis
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DOI：
10.1111/j.1464-410x.2010.09424.x
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发表时间：
2010-12-01
影响因子：
4.5
通讯作者：
Dinney, Colin P. N.
中科院分区：
文献类型：
--
作者：
Black, Peter C.;Shetty, Anil;Dinney, Colin P. N.
ACTERIVETo评估原位膀胱异种移植物的生物发光成像（BLI）与肿瘤体积的相关性，通过磁共振成像（MRI）确定，并定义缺氧和坏死的潜在作用BLI和肿瘤体积之间的关系在adoption.MATERIALS和METHODS原位膀胱肿瘤建立在裸鼠与KU 7和253 J B-V细胞表达荧光素酶。每周进行BLI和MRI检查。根据每个时间点的MR图像计算肿瘤体积。接种后4周和注射吡咪唑后45 min进行尸检。在通过冷冻的整个膀胱标本的1-mm阶梯切片上进行苏木精和伊红染色以及吡咪唑加合物形成的免疫组织化学分析，以分别评估坏死和缺氧。CD 31染色用于评价血管分布。MRI体积和BLI之间的相关性在KU 7异种移植物中弱（R2 < 0.1），但在253 J B-V中强（在4周时R2 = 0.93）。KU 7异种移植物仅在外周具有脉管系统，并显示出广泛的缺氧和坏死区域。减去坏死面积后，BLI与存活肿瘤体积的相关性得到改善（R2 = 0.42）. CONCLUSION肿瘤BLI与肿瘤大小之间的相关性因细胞系而异，在异种移植物中迅速生长超过其血管供应并形成广泛的缺氧和坏死区域。然而，在这些情况下，BLI确实产生了关于存活肿瘤数量的信息，因此仍然应该被认为是一种有用的成像方法。
OBJECTIVETo assess the correlation in orthotopic bladder xenografts of bioluminescence imaging (BLI) with tumour volume as determined by magnetic resonance imaging (MRI), and to define the potential role of hypoxia and necrosis in the relationship between BLI and tumour volume at autopsy.MATERIALS AND METHODSOrthotopic bladder tumours were established in nude mice with KU7 and 253J B-V cells expressing luciferase. BLI and MRI were performed weekly. Tumour volume was calculated from MR images at each time point. Autopsy was performed 4 weeks after inoculation and 45 min after injection of piminidazole. haematoxylin and eosin staining and immunohistochemical analysis of piminidazole adduct formation were performed on 1-mm step-sections through frozen whole bladder specimens to assess necrosis and hypoxia, respectively. CD31 staining was used to evaluate vascularity. Relative volumes of each specimen containing total tumour, hypoxic tumour and necrotic tumour were quantified.RESULTSThe correlation between MRI volume and BLI was weak in KU7 xenografts (R2 < 0.1) but strong in 253J B-V (R2 = 0.93 at 4 weeks). KU7 xenografts had vasculature only peripherally and showed extensive hypoxic and necrotic areas. After subtraction of necrotic areas, the correlation of BLI to viable tumour volume improved (R2 = 0.42).CONCLUSIONThe correlation between tumour BLI and tumour size varies by cell line and is poor in xenografts that rapidly outgrow their vascular supply and develop broad areas of hypoxia and necrosis. However, in these cases BLI does yield information about the amount of viable tumour, and should therefore still be considered as a useful imaging method.