In vivo bioimaging tracks conditionally replicative adenoviral replication and provides an early indication of viral antitumor efficacy.
In vivo bioimaging tracks conditionally replicative adenoviral replication and provides an early indication of viral antitumor efficacy.
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DOI：
10.1111/j.1349-7006.2009.01407.x
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发表时间：
2010-02
期刊：
影响因子：
5.7
通讯作者：
Yamamoto M
中科院分区：
文献类型：
--
作者：
Davydova J;Gavrikova T;Brown EJ;Luo X;Curiel DT;Vickers SM;Yamamoto M
体内监测条件复制腺病毒 (CRAd) 复制并评估其与 CRAd 生物学效应的相关性对于基因治疗的临床开发是必要的。无创生物成像是目前可以监测体内CRAd复制和功能效果的一种方法。在这里，我们描述了一种新型环氧合酶-2 (Cox2) 启动子控制的 CRAd，该 CRAd 被修饰为在其 E3 区域包含萤火虫荧光素酶；这种修饰允许对体外和体内病毒复制进行连续生物发光成像。体外荧光素酶表达与病毒复制和细胞溶解作用相关。体内生物发光成像显示携带皮下肿瘤异种移植物的无胸腺裸鼠中病毒复制水平的动态表现。重要的是，病毒给药后 6 天测量的体内荧光素酶生物发光与第 36 天的 CRAd 抗肿瘤效果显着相关。因此，我们的系统可以检测病毒复制并根据早期成像预测体内治疗结果。这种方法的进一步发展可以提高患者的安全性，加强临床试验的进行，并提供体内 CRAd 功能的机制见解。 （癌症科学 2009 年；00：000–000）
In vivo monitoring of conditionally replicative adenovirus (CRAd) replication and assessing its correlation to CRAd biological effects are necessary for the clinical development of gene therapy. Noninvasive bioimaging is one current approach which can monitor in vivo CRAd replication and functional effect. Here we describe a novel cyclooxygenase-2 (Cox2) promoter-controlled CRAd that was modified to contain firefly luciferase in its E3 region; this modification permitted serial bioluminescence imaging of viral replication in vitro and in vivo. In vitro luciferase expression correlated with viral replication and cytolytic effect. In vivo bioluminescence imaging showed dynamic representation of the viral replication level in athymic nude mice bearing subcutaneous tumor xenografts. Importantly, in vivo luciferase bioluminescence measured 6 days after viral administration significantly correlated with CRAd antitumor effect at day 36. Thus, our system could detect viral replication and predict in vivo therapeutic outcome based on early imaging. Further development of this approach may improve patient safety, enhance clinical trial conduct, and provide mechanistic insight into CRAd function in vivo. (Cancer Sci 2009; 00: 000–000)