Longitudinal live animal micro-CT allows for quantitative analysis of tumor-induced bone destruction.
Longitudinal live animal micro-CT allows for quantitative analysis of tumor-induced bone destruction.
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DOI：
10.1016/j.bone.2010.05.033
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发表时间：
2011-01
期刊：
影响因子：
4.1
通讯作者：
Sterling, Julie A.
中科院分区：
文献类型：
--
作者：
Johnson, Lindsay C.;Johnson, Rachelle W.;Munoz, Steve A.;Mundy, Gregory R.;Peterson, Todd E.;Sterling, Julie A.
大多数患有转移性疾病的乳腺癌和前列腺癌患者将继续发生骨转移，这在很大程度上增加了患者的发病率和死亡率。为了研究肿瘤引起的骨破坏，已经开发了许多癌症骨转移的小动物模型，但用于这些模型的成像方式的进步明显落后于临床成像。因此，迫切需要改进活体小动物成像，特别是在获得用于纵向定量分析的高分辨率图像时。最近，活体动物微型计算机断层扫描 (μCT) 由于能够获得高分辨率的 3 维图像而受到欢迎。然而，由于肿瘤细胞的脱靶放射效应，μCT 在骨转移模型中的应用仅限于终点分析。我们假设活体动物体内 μCT 可用于对荷瘤小鼠的骨体积进行可重复和定量的纵向分析，特别是在乳腺癌骨转移的药物治疗模型中。为了检验这一假设，我们利用 MDA-MB-231 溶骨性乳腺癌模型，将肿瘤细胞直接接种到无胸腺裸鼠的胫骨中，并每周通过 Faxitron（放射线照相）、Imtek μCT（体内）和 Maestro（GFP 成像）对小鼠进行成像。在终点时进行离体 μCT 和组织学检查以进行验证。在为 Imtek CT 建立高分辨率扫描方案后，我们确定在接受双膦酸盐药物治疗的小鼠中是否可以检测到明显的、可测量的骨体积差异。我们发现体内 μCT 可用于获得骨破坏随时间进展的可量化纵向图像，而不会改变肿瘤细胞的生长。此外，我们发现我们早在第一周就可以检测到病变，并且这种方法可用于监测药物治疗对骨骼的影响。综上所述，这些数据表明体内 μCT 是一种有效且可重复的方法，可用于纵向监测肿瘤诱发骨病小鼠模型中肿瘤相关骨破坏。
The majority of breast cancer and prostate cancer patients with metastatic disease will go on to develop bone metastases, which contribute largely to patient morbidity and mortality. Numerous small animal models of cancer metastasis to bone have been developed in order to study tumor-induced bone destruction, but the advancement of imaging modalities utilized for these models has lagged significantly behind clinical imaging. Therefore, there is a significant need for improvements to live small animal imaging, particularly when obtaining high resolution images for longitudinal quantitative analyses. Recently, live animal micro-Computed Tomography (μCT) has gained popularity due to the ability to obtain high resolution, 3-dimensional images. However, the utility of μCT in bone metastasis models has been limited to end-point analyses due to off-target radiation effects on tumor cells. We hypothesized that live animal in vivo μCT can be utilized to perform reproducible and quantitative longitudinal analyses of bone volume in tumor bearing mice, particularly in a drug treatment model of breast cancer metastasis to bone. To test this hypothesis we utilized the MDA-MB-231 osteolytic breast cancer model in which the tumor cells are inoculated directly into the tibia of athymic nude mice and imaged mice weekly by Faxitron (radiography), Imtek μCT (in vivo), and Maestro (GFP-imaging). Ex-vivo μCT and histology were performed at end-point for validation. After establishing a high resolution scanning protocol for the Imtek CT, we determined whether clear, measurable differences in bone volume were detectable in mice undergoing bisphosphonate drug treatments. We found that in vivo μCT can be used to obtain quantifiable and longitudinal images of the progression of bone destruction over time without altering tumor cell growth. Additionally, we found that we could detect lesions as early as week one and that this approach could be used to monitor the effect of drug treatment on bone. Taken together, these data indicate in vivo μCT is an effective and reproducible method for longitudinal monitoring of tumor-associated bone destruction in mouse models of tumor-induced bone disease.
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