Visualization of advanced human prostate cancer lesions in living mice by a targeted gene transfer vector and optical imaging

Visualization of advanced human prostate cancer lesions in living mice by a targeted gene transfer vector and optical imaging
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DOI:
10.1038/nm743
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发表时间:
2002-08-01
期刊:
影响因子:
82.9
通讯作者:
Wu, L
Wu, L
中科院分区:
医学1区
文献类型:
--
作者:
Adams, JY;Johnson, M;Wu, L

文献摘要

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非侵入性成像和转录靶向可以提高癌症治疗方法的安全性。在这里,我们证明了在人前列腺癌模型中识别转移的能力,采用前列腺特异性腺病毒载体(AdPSE BC-luc)和电荷耦合器件成像系统。AdPSE-BC-luc从增强的前列腺特异性抗原启动子表达萤火虫荧光素酶,限制了在肝脏中的表达,但在前列腺肿瘤中产生了强大的信号。事实上,在晚期雄激素非依赖性肿瘤中的表达高于雄激素依赖性病变。在将AdPSE-BC-luc注射到荷瘤小鼠中后三周内的重复成像显示,该病毒可以定位并照亮肺和脊柱中的转移灶。全身注射低剂量的AdPSE-BC-luc照亮肺转移。这些结果表明,潜在的使用非侵入性成像方式在治疗和诊断策略,以管理前列腺癌。
Non-invasive imaging and transcriptional targeting can improve the safety of therapeutic approaches in cancer. Here we demonstrate the ability to identify metastases in a human-prostate cancer model, employing a prostate-specific adenovirus vector (AdPSE-BC-luc) and a charge-coupled device-imaging system. AdPSE-BC-luc, which expresses firefly luciferase from an enhanced prostate-specific antigen promoter, restricted expression in the liver but produced robust signals in prostate tumors. In fact, expression was higher in advanced, androgen-independent tumors than in androgen-dependent lesions. Repetitive imaging over a three-week period after AdPSE-BC-luc injection into tumor-bearing mice revealed that the virus could locate and illuminate metastases in the lung and spine. Systemic injection of low doses of AdPSE-BC-luc illuminated lung metastasis. These results demonstrate the potential use of a non-invasive imaging modality in therapeutic and diagnostic strategies to manage prostate cancer.