64Cu-DOTA-anti-CTLA-4 mAb enabled PET visualization of CTLA-4 on the T-cell infiltrating tumor tissues.
64Cu-DOTA-anti-CTLA-4 mAb enabled PET visualization of CTLA-4 on the T-cell infiltrating tumor tissues.
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DOI：
10.1371/journal.pone.0109866
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Enomoto S
中科院分区：
文献类型：
--
作者：
Higashikawa K;Yagi K;Watanabe K;Kamino S;Ueda M;Hiromura M;Enomoto S
抗细胞毒性T淋巴细胞相关抗原4（CTLA-4）单克隆抗体（mAb）靶向治疗恶性肿瘤疗效显著。然而，它极其昂贵，并且可能产生与自身免疫相关的不良反应。因此，开发一种在CTLA-4靶向治疗之前评估CTLA-4表达的方法有望为循证和成本效益高的医疗保健打开大门，并避免无效治疗带来的不良反应。本研究的目的是研制一种CTLA-4分子成像探针，用于肿瘤组织中CTLA-4的显像。首先，我们通过逆转录聚合酶链反应（RT-PCR）分析检测了CTLA-4在正常结肠组织、培养的CT26细胞以及来自荷瘤BALB/c小鼠和BALB/c裸鼠的CT26肿瘤组织中的表达，并确认了CTLA-4是否在CT26肿瘤组织中强表达。第二，我们合成了64 Cu-1，4，7，10-四氮杂环十二烷-N，N ′，N ″，N ′-四乙酸-抗小鼠CTLA-4单克隆抗体（64 Cu-DOTA-anti-CTLA-4 mAb），并评价了其在正电子发射断层扫描（PET）和离体生物分布分析中的应用。在荷瘤BALB/c小鼠的CT26肿瘤组织中证实了CTLA-4的高表达。而CTLA-4在体外培养的CT26细胞及荷瘤BALB/c裸鼠的CT26肿瘤组织中表达极低。结果表明，T细胞是导致CTLA-4高表达的原因。此外，64Cu-DOTA-抗CTLA-4 mAb在CT26肿瘤中显示出显著高的积累，从而实现了肿瘤中的非侵入性CTLA-4可视化。总之，结果表明，64Cu-DOTA-抗CTLA-4 mAb可用于评估肿瘤中CTLA-4的表达。
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) targeted therapy by anti-CTLA-4 monoclonal antibody (mAb) is highly effective in cancer patients. However, it is extremely expensive and potentially produces autoimmune-related adverse effects. Therefore, the development of a method to evaluate CTLA-4 expression prior to CTLA-4-targeted therapy is expected to open doors to evidence-based and cost-efficient medical care and to avoid adverse effects brought about by ineffective therapy. In this study, we aimed to develop a molecular imaging probe for CTLA-4 visualization in tumor. First, we examined CTLA-4 expression in normal colon tissues, cultured CT26 cells, and CT26 tumor tissues from tumor-bearing BALB/c mice and BALB/c nude mice by reverse transcription polymerase chain reaction (RT-PCR) analysis and confirmed whether CTLA-4 is strongly expressed in CT26 tumor tissues. Second, we newly synthesized 64Cu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-anti-mouse CTLA-4 mAb (64Cu-DOTA-anti-CTLA-4 mAb) and evaluated its usefulness in positron emission tomography (PET) and ex-vivo biodistribution analysis in CT26-bearing BALB/c mice. High CTLA-4 expression was confirmed in the CT26 tumor tissues of tumor-bearing BALB/c mice. However, CTLA-4 expression was extremely low in the cultured CT26 cells and the CT26 tumor tissues of tumor-bearing BALB/c nude mice. The results suggested that T cells were responsible for the high CTLA-4 expression. Furthermore, 64Cu-DOTA-anti-CTLA-4 mAb displayed significantly high accumulation in the CT26 tumor, thereby realizing non-invasive CTLA-4 visualization in the tumor. Together, the results indicate that 64Cu-DOTA-anti-CTLA-4 mAb would be useful for the evaluation of CTLA-4 expression in tumor.
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影响因子：
7.7
作者：
Gerold KD;Zheng P;Rainbow DB;Zernecke A;Wicker LS;Kissler S
通讯作者：
Kissler S
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
5.7
作者：
Paudyal, Bishnuhari;Paudyal, Pramila;Endo, Keigo
通讯作者：
Endo, Keigo
影响因子：
32.4
作者：
Vijayakrishnan, L;Slavik, JM;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
120.1
作者：
Sondak, Vernon K.;Smalley, Keiran S. M.;Kirkpatrick, Peter
通讯作者：
Kirkpatrick, Peter