Anti-tumor effect of integrin targeted (177)Lu-3PRGD2 and combined therapy with Endostar.
Anti-tumor effect of integrin targeted (177)Lu-3PRGD2 and combined therapy with Endostar.
复制标题
整合素靶向(177)Lu-3PRGD2及与恩度联合治疗的抗肿瘤作用。
作者：
Shi J;Fan D;Dong C;Liu H;Jia B;Zhao H;Jin X;Liu Z;Li F;Wang F
目的：靶向放射治疗（TRT）是一种新兴的肿瘤治疗方法。先前，3 PRGD 2（具有3个PEG 4接头的二聚体RGD肽）已被证明对于整联蛋白αvβ3靶向是有利的。鉴于99 mTc-3 PRGD 2用于人类肺癌检测的有希望的结果，我们被鼓励研究放射性标记的3 PRGD 2的放射治疗功效。本研究的目的是在动物模型中研究和优化整合素αvβ3介导的177 Lu-3 PRGD 2的治疗作用。实验设计：进行177 Lu-3 PRGD 2的生物分布、γ成像和最大耐受剂量（MTD）研究。对U87 MG肿瘤模型进行单次、多次靶向放疗（TRT）及TRT与恩度抗血管生成治疗（AAT）的联合治疗。治疗后行苏木精-伊红（H&E）染色及免疫组化（IHC）观察疗效。结果如下：U87 MG肿瘤对177 Lu-3 PRGD 2的摄取相对较高（注射后1 h、4 h、24 h和72 h分别为6.03 ± 0.65% ID/g、4.62 ± 1.44% ID/g、3.55 ± 1.08% ID/g和1.22 ± 0.18% ID/g），并且γ成像可以清楚地显示肿瘤。177 Lu-3 PRGD 2在裸鼠中的MTD（>111 MBq）是90 Y-3 PRGD 2（55.5MBq）的两倍。U87 MG肿瘤生长被177 Lu-3 PRGD 2 TRT显著延迟。在两个剂量或联合治疗组中观察到显著增加的抗肿瘤作用。结论：TRT两次给药和与恩度联合治疗有效地增强了肿瘤生长抑制，但前者不需要连续数周每天注射，避免了许多不必要的不便和患者的痛苦，这可能在未来迅速转化为临床实践。
Purpose: Targeted radiotherapy (TRT) is an emerging approach for tumor treatment. Previously, 3PRGD2 (a dimeric RGD peptide with 3 PEG4 linkers) has been demonstrated to be of advantage for integrin αvβ3 targeting. Given the promising results of 99mTc-3PRGD2 for lung cancer detection in human beings, we are encouraged to investigate the radiotherapeutic efficacy of radiolabeled 3PRGD2. The goal of this study was to investigate and optimize the integrin αvβ3 mediated therapeutic effect of 177Lu-3PRGD2 in the animal model. Experimental Design: Biodistribution, gamma imaging and maximum tolerated dose (MTD) studies of 177Lu-3PRGD2 were performed. The targeted radiotherapy (TRT) with single dose and repeated doses as well as the combined therapy of TRT and the anti-angiogenic therapy (AAT) with Endostar were conducted in U87MG tumor model. The hematoxylin and eosin (H&E) staining and immunochemistry (IHC) were performed post-treatment to evaluate the therapeutic effect. Results: The U87MG tumor uptake of 177Lu-3PRGD2 was relatively high (6.03 ± 0.65 %ID/g, 4.62 ± 1.44 %ID/g, 3.55 ± 1.08 %ID/g, and 1.22 ± 0.18 %ID/g at 1 h, 4 h, 24 h, and 72 h postinjection, respectively), and the gamma imaging could visualize the tumors clearly. The MTD of 177Lu-3PRGD2 in nude mice (>111 MBq) was twice to that of 90Y-3PRGD2 (55.5 MBq). U87MG tumor growth was significantly delayed by 177Lu-3PRGD2 TRT. Significantly increased anti-tumor effects were observed in the two doses or combined treatment groups. Conclusion: The two-dose TRT and combined therapy with Endostar potently enhanced the tumor growth inhibition, but the former does not need to inject daily for weeks, avoiding a lot of unnecessary inconvenience and suffering for patients, which could potentially be rapidly translated into clinical practice in the future.
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影响因子：
6.2
作者：
Delaney, G;Jacob, S;Barton, M
通讯作者：
Barton, M
重组人内皮抑素使异种移植人鼻咽癌模型中的肿瘤血管正常化并增强放射反应
影响因子：
3.7
作者：
Peng F;Xu Z;Wang J;Chen Y;Li Q;Zuo Y;Chen J;Hu X;Zhou Q;Wang Y;Ma H;Bao Y;Chen M
通讯作者：
Chen M
影响因子：
1.8
作者：
Luna-Gutierrez, Myrna;Ferro-Flores, Guillermina;Isaac-Olive, Keila
通讯作者：
Isaac-Olive, Keila
影响因子：
11.5
作者：
Lee, FT;Mountain, AJ;Scott, AM
通讯作者：
Scott, AM
影响因子：
11.5
作者：
Schmidt, NO;Ziu, M;Carroll, RS
通讯作者：
Carroll, RS