Optical Imaging of cancer metastasis to bone marrow -: A mouse model of minimal residual disease

Optical Imaging of cancer metastasis to bone marrow -: A mouse model of minimal residual disease
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DOI:
10.1016/s0002-9440(10)64934-6
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发表时间:
2002-03-01
影响因子:
6
通讯作者:
Cecchini, MG
Cecchini, MG
中科院分区:
医学2区
文献类型:
--
作者:
Wetterwald, A;van der Pluijm, G;Cecchini, MG

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新的抗癌策略的发展需要更灵敏和更少侵入性的方法来检测和监测体内癌症模型中的微小残留疾病。骨髓转移通过放射学间接检测为溶骨性和/或骨硬化性病变。骨髓微转移瘤不能进行放射学检测,因此需要更灵敏的方法来直接鉴定。将癌细胞注入小鼠的左心室,可以很好地模拟微转移扩散。当使用荧光素酶转基因细胞时,全身生物发光报告成像可以检测到体积约为0.5 mm(3)的微小骨髓转移瘤,这个体积低于肿瘤需要诱导血管生成以进一步生长的极限。这种敏感性转化为早期检测到髓内肿瘤的生长,比放射学上明显的骨溶解早了大约2周。生物发光报告成像还可以在同一动物中持续监测每个转移部位的生长动力学,并指导终点分析,特别是对受转移生长影响的骨骼进行分析。这一模型将促进对转移中的分子事件的理解和旨在抑制转移生长初期阶段的新疗法的评估。
The development of novel anti-cancer strategies requires more sensitive and less invasive methods to detect and monitor in vivo minimal residual disease in cancer models. Bone marrow metastases are indirectly detected by radiography as osteolytic and/or osteosclerotic lesions. Marrow micrometastases elude radiographic detection and, therefore, more sensitive methods are needed for their direct identification. injection of cancer cells into the left cardiac ventricle of mice closely mimics micrometastatic spread. When luciferase-transfected cells are used, whole-body bioluminescent reporter imaging can detect microscopic bone marrow metastases of approximate to0.5 mm(3) volume, a size below the limit in which tumors need to induce angiogenesis for further growth. This sensitivity translates into early detection of intramedullary tumor growth, preceding the appearance of a radiologically evident osteolysis by approximate to2 weeks. Bioluminescent reporter imaging also enables continuous monitoring in the same animal of growth kinetics for each metastatic site and guides end-point analyses specifically to the bones affected by metastatic growth. This model will accelerate the understanding of the molecular events in metastasis and the evaluation of novel therapies aiming at repressing initial stages of metastatic growth.