Monitoring the initial delivery of an oncolytic measles virus encoding the human sodium iodide symporter to solid tumors using contrast-enhanced computed tomography.

Monitoring the initial delivery of an oncolytic measles virus encoding the human sodium iodide symporter to solid tumors using contrast-enhanced computed tomography.
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DOI:
10.1002/jgm.2670
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发表时间:
2012-09
影响因子:
3.5
通讯作者:
Carlson, Stephanie K.
Carlson, Stephanie K.
中科院分区:
医学4区
文献类型:
--
作者:
Penheiter, Alan R.;Dingli, David;Bender, Claire E.;Russell, Stephen J.;Carlson, Stephanie K.

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我们的目的是确定利用碘化造影剂和微计算机断层扫描(CT)监测病毒在实体瘤中的传递和初始分布的可行性。在裸鼠体内建立人BxPC-3胰腺肿瘤异种移植物。将一种具有额外编码碘化钠同调体(NIS)转录单位的溶瘤性麻疹病毒与1:10稀释的Omnipaque 300 (GE Healthcare, Milwaukee, WI, USA)造影剂混合,直接注射到肿瘤中。在注射前后立即对小鼠进行micro-CT成像,确定对比剂/病毒混合物的位置。注射后第3天再次对小鼠进行微单光子发射CT/CT成像,以确定nis介导的99mTcO4转运的位置。1:10的Omnipaque稀释对体外病毒感染性和细胞活力没有影响,对于肿瘤内注射分布的CT成像来说已经足够了。初始CT造影剂覆盖的肿瘤体积与感染后3天的病毒感染肿瘤体积测量有显著相关性。此外,未接受初始注射造影剂的肿瘤区域在早期时间点基本上没有病毒感染。对比增强的病毒传递能够快速准确地预测实体瘤内的初始病毒分布。这项技术应该能够实时监测病毒从最初感染的肿瘤区域到邻近肿瘤区域的传播情况。
We aimed to determine the feasibility of monitoring viral delivery and initial distribution to solid tumors using iodinated contrast agent and micro-computed tomography (CT). Human BxPC-3 pancreatic tumor xenografts were established in nude mice. An oncolytic measles virus with an additional transcriptional unit encoding the sodium iodide symporter (NIS), as a reporter for viral infection, was mixed with a 1:10 dilution of Omnipaque 300 (GE Healthcare, Milwaukee, WI, USA) contrast agent and injected directly into tumors. Mice were imaged with micro-CT immediately before and after injection to determine the location of contrast agent/virus mixture. Mice were imaged again on day 3 after injection with micro-single-photon emission CT/CT to determine the location of NIS-mediated 99mTcO4 transport. A 1:10 dilution of Omnipaque had no effect on viral infectivity or cell viability in vitro and was more than adequate for CT imaging of the intratumoral injectate distribution. The volume of tumor coverage with initial CT contrast agent and the 3-day postinfection measurement of virally infected tumor volume were significantly correlated. Additionally, regions of the tumor that did not receive contrast agent from the initial injection were largely devoid of viral infection at early time points. Contrast-enhanced viral delivery enables a rapid and accurate prediction of the initial viral distribution within a solid tumor. This technique should enable real-time monitoring of viral propagation from initially infected tumor regions to adjacent tumor regions.
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