Evaluation of 64Cu labeled GX1: a phage display peptide probe for PET imaging of tumor vasculature.
Evaluation of 64Cu labeled GX1: a phage display peptide probe for PET imaging of tumor vasculature.
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64Cu 标记 GX1 的评估：用于肿瘤脉管系统 PET 成像的噬菌体展示肽探针。
DOI：
10.1007/s11307-011-0479-1
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发表时间：
2012-02
影响因子：
3.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Chen, Kai;Sun, Xilin;Niu, Gang;Ma, Ying;Yap, Li-Peng;Hui, Xiaoli;Wu, Kaichun;Fan, Daiming;Conti, Peter S.;Chen, Xiaoyuan
使用靶向肿瘤血管的正电子发射断层扫描（PET）放射性示踪剂的分子成像提供了一种用于早期检测肿瘤血管生成和有效监测抗肿瘤血管治疗反应的非侵入性方法。先前的体外研究结果表明，通过噬菌体展示技术鉴定的GX 1肽是肿瘤血管内皮特异性配体。在这项研究中，我们评估了64 Cu标记的GX 1肽作为一种潜在的放射性示踪剂，用于U87 MG肿瘤异种移植小鼠模型中肿瘤血管的microPET成像。合成了大环螯合剂1，4，7，10-四氮杂环十二烷-N，N′，N″，N ′-四乙酸（DOTA）偶联GX 1肽，并在乙酸铵缓冲液中用64 Cu（t1/2=12.7 h）进行放射性标记。然后在U87 MG肿瘤异种移植小鼠模型中对64 Cu标记的GX 1肽进行体外肿瘤细胞摄取研究、小动物PET和直接组织取样生物分布研究。体外实验证明64 Cu-DOTA-GX 1在PBS中是稳定的，在孵育24小时后超过91%的64 Cu-DOTA-GX 1肽保持完整。细胞摄取和保留研究显示，64 Cu-DOTA-GX 1与U87 MG胶质瘤细胞结合，并具有良好的肿瘤细胞保留。对于小动物PET成像研究，在注射64 Cu-DOTA-GX 1后的所有测量时间点，U87 MG肿瘤都清晰可见，与对侧背景具有高对比度，而在早期时间点也观察到肝脏和肾脏中的高积累。U87 MG肿瘤摄取在感染后24小时测定为最高（7.97±0.75%ID/g）。通过在注射后24小时共注射64 Cu-DOTA-GX 1与非放射性标记的GX 1肽（20 mg/kg）来实现阻断实验，表明64 Cu-DOTA-GX 1是靶特异性示踪剂。此外，生物分布结果与microPET成像的定量一致，表明非阻断组在24 h pi的肿瘤/肌肉摄取64 Cu-DOTA-GX 1的比率最高（16.09±1.21），而阻断组的比率显著降低（6.57±0.58）。最后，代谢研究表明，64 Cu-DOTA-GX 1在体内早期时间点在小鼠血液和尿液中是稳定的，而金属螯合转移也可能发生在小鼠肝脏和肾脏中。我们的研究表明，64 Cu-DOTA-GX 1是一种有前途的肿瘤血管成像放射性示踪剂。
Molecular imaging using positron emission tomography (PET) radiotracers targeted to tumor vasculature offers a noninvasive method for early detection of tumor angiogenesis and efficient monitoring of response to anti-tumor vasculature therapy. The previous in vitro results demonstrated that the GX1 peptide, identified by phage display technology, is a tumor vasculature endothelium-specific ligand. In this study, we evaluated a 64Cu-labeled GX1 peptide as a potential radiotracer for microPET imaging of tumor vasculature in a U87MG tumor xenografted mouse model. Macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-N, N′, N″, N‴-tetraacetic acid (DOTA)-conjugated GX1 peptide was synthesized and radiolabeled with 64Cu (t1/2=12.7 h) in ammonium acetate buffer. The 64Cu-labeled GX1 peptide was then subjected to in vitro tumor cell uptake study, small animal PET and direct tissue sampling biodistribution studies in a U87MG tumor xenografted mouse model. The in vitro experiment demonstrated that 64Cu-DOTA-GX1 is stable in PBS with more than 91% of 64Cu-DOTA-GX1 peptide remaining intact after 24 h of incubation. Cellular uptake and retention studies revealed 64Cu-DOTA-GX1 binds to U87MG glioma cells and has good tumor cell retention. For small animal PET imaging studies, the U87MG tumors were all clearly visible with high contrast to contralateral background at all measured time points after injection of 64Cu-DOTA-GX1 while high accumulation in liver and kidneys were also observed at early time points. The U87MG tumor uptake was determined to be the highest (7.97±0.75%ID/g) at 24 h pi. The blocking experiment was achieved by co-injection of 64Cu-DOTA-GX1 with non-radiolabeled GX1 peptide (20 mg/kg) at 24 h pi, suggesting 64Cu-DOTA-GX1 is a target-specific tracer. Furthermore, the biodistribution results were consistent with the quantification of microPET imaging, demonstrating the highest ratio (16.09±1.21) of tumor/muscle uptake of 64Cu-DOTA-GX1 at 24 h pi for non-blocking group and significant decreased ratio (6.57±0.58) for blocking group. Finally, metabolic studies suggested that 64Cu-DOTA-GX1 is stable in mouse blood and urine in vivo at early time point while the metal transchelation may also occur in mouse liver and kidneys. Our studies demonstrate that 64Cu-DOTA-GX1 is a promising radiotracer for imaging tumor vasculature.
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影响因子：
62.1
作者：
Deutscher, Susan L.
通讯作者：
Deutscher, Susan L.
DOI：
10.1158/1078-0432.ccr-10-0968
发表时间：
2010-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Sun X;Niu G;Yan Y;Yang M;Chen K;Ma Y;Chan N;Shen B;Chen X
通讯作者：
Chen X
DOI：
10.1007/s00259-009-1123-z
发表时间：
2009-09-01
影响因子：
9.1
作者：
Liu, Zhaofei;Niu, Gang;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
影响因子：
3.1
作者：
Chen, XY;Liu, S;Conti, PS
通讯作者：
Conti, PS
影响因子：
4.7
作者：
Shi J;Kim YS;Zhai S;Liu Z;Chen X;Liu S
通讯作者：
Liu S