Quantitative PET reporter gene imaging of CD8+ T cells specific for a melanoma-expressed self-antigen.
Quantitative PET reporter gene imaging of CD8+ T cells specific for a melanoma-expressed self-antigen.
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DOI：
10.1093/intimm/dxn133
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发表时间：
2009-02
影响因子：
4.4
通讯作者：
Witte ON
中科院分区：
文献类型：
--
作者：
Shu CJ;Radu CG;Shelly SM;Vo DD;Prins R;Ribas A;Phelps ME;Witte ON
过继性转移（AT） t细胞治疗为晚期黑色素瘤患者提供了显著的临床益处。然而，目前缺乏非侵入性观察转移T细胞持久性的方法。我们研究了正电子发射断层扫描（PET）是否可以监测表达单纯疱疹病毒1胸苷激酶（sr39tk） PET报告基因的自身抗原特异性T细胞的分布。使用sr39tk特异性底物9-[4-[18F]氟-3-（羟甲基）-丁基]鸟嘌呤（[18F]FHBG）进行微pet成像，可以在3周内检测到受体小鼠次级淋巴器官中移植的T细胞。与对照组相比，在接受联合免疫治疗的小鼠中，脾脏的微pet信号增加了约25倍，淋巴结（LNs）增加了2倍，肿瘤反应早在AT后3天就可以预测。脾脏的检测下限为~ 7 × 105个T细胞，LNs为1 × 104个T细胞。肿瘤中移植T细胞的定量受到sr39tk不依赖于[18F]FHBG在肿瘤结构中的捕获的阻碍。这些数据支持使用PET可视化转移T细胞的扩增、归巢和持久性的可行性。PET可以提供量化全身抗肿瘤T细胞的方法，并为治疗效果提供早期相关性，从而具有重要的临床应用价值。
Adoptive transfer (AT) T-cell therapy provides significant clinical benefits in patients with advanced melanoma. However, approaches to non-invasively visualize the persistence of transferred T cells are lacking. We examined whether positron emission tomography (PET) can monitor the distribution of self-antigen-specific T cells engineered to express an herpes simplex virus 1 thymidine kinase (sr39tk) PET reporter gene. Micro-PET imaging using the sr39tk-specific substrate 9-[4-[18F]fluoro-3-(hydroxymethyl)-butyl]guanine ([18F]FHBG) enabled the detection of transplanted T cells in secondary lymphoid organs of recipient mice over a 3-week period. Tumor responses could be predicted as early as 3 days following AT when a >25-fold increase of micro-PET signal in the spleen and 2-fold increase in lymph nodes (LNs) were observed in mice receiving combined immunotherapy versus control mice. The lower limit of detection was ∼7 × 105 T cells in the spleen and 1 × 104 T cells in LNs. Quantification of transplanted T cells in the tumor was hampered by the sr39tk-independent trapping of [18F]FHBG within the tumor architecture. These data support the feasibility of using PET to visualize the expansion, homing and persistence of transferred T cells. PET may have significant clinical utility by providing the means to quantify anti-tumor T cells throughout the body and provide early correlates for treatment efficacy.
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影响因子：
29.4
作者：
Peñuelas, I;Mazzolini, G;Prieto, J
通讯作者：
Prieto, J
影响因子：
14.8
作者：
Pittet, Mikael J.;Swirski, Filip K.;Weissleder, Ralph
通讯作者：
Weissleder, Ralph
影响因子：
11.5
作者：
Comin-Anduix, B;Gualberto, A;Ribas, A
通讯作者：
Ribas, A
影响因子：
9.3
作者：
Ponomarev, Vladimir;Doubrovin, Michael;Gelovani, Juri
通讯作者：
Gelovani, Juri
DOI：
10.1084/jem.20030590
发表时间：
2003-08-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Overwijk WW;Theoret MR;Finkelstein SE;Surman DR;de Jong LA;Vyth-Dreese FA;Dellemijn TA;Antony PA;Spiess PJ;Palmer DC;Heimann DM;Klebanoff CA;Yu Z;Hwang LN;Feigenbaum L;Kruisbeek AM;Rosenberg SA;Restifo NP
通讯作者：
Restifo NP