Theranostics 2014; 4(3):256-266. doi:10.7150/thno.7781

Research Paper

Anti-tumor Effect of Integrin Targeted 177Lu-3PRGD2 and Combined Therapy with Endostar

Jiyun Shi1,2, Di Fan1,3, Chengyan Dong1,3, Hao Liu1,3, Bing Jia1,3, Huiyun Zhao1,2, Xiaona Jin4, Zhaofei Liu1,3, Fang Li4, Fan Wang1,3✉

1. Medical Isotopes Research Center, Peking University, Beijing 100191, China;
2. Medical and Healthy Analytical Center, Peking University, Beijing 100191, China;
3. Department of Radiation Medicine, Basic Medical Sciences, Peking University, Beijing 100191, China;
4. Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing 100857, China.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Shi J, Fan D, Dong C, Liu H, Jia B, Zhao H, Jin X, Liu Z, Li F, Wang F. Anti-tumor Effect of Integrin Targeted 177Lu-3PRGD2 and Combined Therapy with Endostar. Theranostics 2014; 4(3):256-266. doi:10.7150/thno.7781. Available from

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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.

Keywords: Integrin αvβ3, Arg-Gly-Asp (RGD), 177Lu, radionuclide therapy, combination therapy.