Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients
Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients
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DOI：
10.1053/j.gastro.2005.03.024
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发表时间：
2005-06-01
期刊：
影响因子：
29.4
通讯作者：
Prieto, J
中科院分区：
文献类型：
--
作者：
Peñuelas, I;Mazzolini, G;Prieto, J
背景与目的：在基因治疗方案中，需要对基因表达进行成像，以评估载体的转导效率、组织分布和转基因表达的持续时间，并评估重复给药的可行性。方法：我们使用正电子发射断层扫描和氟-18标记的喷昔洛韦类似物来监测第一代重组腺病毒瘤内注射后肝细胞癌患者胸苷激酶基因的表达。患者参加了一项试点临床试验，并使用递增剂量的载体进行治疗。在腺病毒接种两天后，在给药后的第一个小时内，在治疗的皮损和全身的基础上评估转基因表达。结果：转基因在肿瘤中的表达依赖于腺病毒的注射剂量，并且在所有接受：：1012病毒颗粒的患者中都能检测到。然而，当载体注射后第9天重复研究时，没有观察到表达。有趣的是，在所研究的任何病例中，在远处的器官或周围的肝硬变组织中都没有检测到转基因的特定表达。结论：我们的研究结果显示了利用病毒载体在人类体内进行转基因表达成像的真正可能性。我们发现，肝癌是腺病毒感染的许可肿瘤，当通过瘤内注射载体时，非肿瘤性肝硬变的肝脏免于转导。这些结果表明，正电子发射断层成像可能有助于基因治疗策略的设计和新一代载体的临床评估。
Background & Aims: In gene-therapy protocols, imaging of gene expression is needed to evaluate the transduction efficiency of the vector, its tissue distribution, and the duration of transgene expression and to assess the feasibility of repeated vector administration. Methods: We have used positron emission tomography with a fluorine-18-labeled penciclovir analogue to monitor thymidine kinase gene expression after intratumoral injection of a first-generation recombinant adenovirus in patients with hepatocellular carcinoma. Patients were enrolled in a pilot clinical trial and treated with escalating doses of the vector. Two days after adenovirus inoculation, transgene expression was evaluated during the first hours after administration of the radiotracer both on the treated lesion and on a whole-body basis. Results: Transgene expression in the tumor was dependent on the injected dose of the adenovirus and was detectable in all patients who received ::1012 viral particles. However, when the study was repeated 9 days after vector injection, no expression could be observed. It is interesting to note that no specific expression of the transgene could be detected in distant organs or in the surrounding cirrhotic tissue in any of the cases studied. Conclusions: Our findings show the real possibility of imaging transgene expression in humans by using viral vectors. We show that hepatocarcinoma is a permissive tumor for adenoviral infection and that the nontumoral cirrhotic liver is spared from transduction when the vector is administered by intratumoral injection. These results show that positron emission tomography imaging may help in the design of gene-therapy strategies and in the clinical assessment of new-generation vectors.