Repetitive Noninvasive Monitoring of HSV1-tk-Expressing T Cells Intravenously Infused into Nonhuman Primates Using Positron Emission Tomography and Computed Tomography with 18F-FEAU
Repetitive Noninvasive Monitoring of HSV1-tk-Expressing T Cells Intravenously Infused into Nonhuman Primates Using Positron Emission Tomography and Computed Tomography with 18F-FEAU
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DOI：
10.2310/7290.2009.00022
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发表时间：
2009-07-01
影响因子：
2.8
通讯作者：
Gelovani, Juri G.
中科院分区：
文献类型：
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作者：
Dotti, Gianpietro;Tian, Mei;Gelovani, Juri G.
抗原特异性细胞毒性T淋巴细胞（CTL）的连续转移已成功用于治疗患有不同类型癌症的患者。然而，全身输注的CTL的分布的长期时空动态在很大程度上仍然未知。采用分子遗传学报告成像与正电子发射断层扫描和计算机断层扫描（PET-CT）的过继转移的CTL的非侵入性成像代表了理解过继转移的T细胞的长期迁移模式和治疗潜力的创新方法。在这里，我们报告的应用重复PET-CT成像与[F-18]氟-5-乙基-1-β-D-阿拉伯呋喃尿嘧啶（F-18-FEAU），证明自体多克隆猕猴T淋巴细胞活化并用编码sr 39突变型单纯疱疹病毒1胸苷激酶的逆转录病毒载体转导（sr 39 HSV 1-tk）报告基因可在静脉内输注后在离散的淋巴器官和炎症部位中检测到。该研究代表了原理证明，并支持F-18-FEAU PET-CT成像用于监测静脉内施用的sr 39 HSV 1-tk基因转导的CTL在人体中的分布。
Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) has been successfully used to treat patients with different types of cancer. However, the long-term spatial-temporal dynamics of the distribution of systemically infused CTLs remains largely unknown. Noninvasive imaging of adoptively transferred CTLs using molecular-genetic reporter imaging with positron emission tomography and computed tomography (PET-CT) represents an innovative approach to understanding the long-term migratory patterns and therapeutic potential of adoptively transferred T cells. Here we report the application of repetitive PET-CT imaging with [F-18]fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil (F-18-FEAU) in two nonhuman primates demonstrating that autologous polyclonal macaque T lymphocytes activated and transduced with a retroviral vector encoding for the sr39 mutant herpes simplex virus 1 thymidine kinase (sr39HSV1-tk) reporter gene can be detected after intravenous infusion in discrete lymphoid organs and in sites of inflammation. This study represents a proof of principle and supports the application of F-18-FEAU PET-CT imaging for monitoring the distribution of intravenously administered sr39HSV1-tk gene-transduced CTLs in humans.