First-in-human study of 177Lu-EB-PSMA-617 in patients with metastatic castration-resistant prostate cancer

  • Jie Zang
  • Xinrong Fan
  • Hao Wang
  • Qingxing Liu
  • Jingnan Wang
  • Hui Li
  • Fang Li
  • Orit Jacobson
  • Gang Niu
  • Zhaohui ZhuEmail author
  • Xiaoyuan ChenEmail author
Original Article



This translational study is designed to assess the safety, dosimetry and therapeutic response to a single, low-dose of 177Lu-EB-PSMA-617 in comparison to 177Lu-PSMA-617 in patients with mCRPC.


Following institutional review board approval and informed consent, nine patients with mCRPC were recruited. Four patients accepted intravenous injection of 0.80–1.1 GBq (21.5–30 mCi) of 177Lu-EB-PSMA-617, then underwent serial whole-body planar and SPECT/CT imaging at 2, 24, 72, 120 and 168 h. The other five patients accepted intravenous injection of 1.30–1.42 GBq (35–38.4 mCi) 177Lu-PSMA-617, then underwent the same imaging procedures at 0.5, 2, 24, 48, and 72 h. All patients were evaluated by 68Ga-PSMA-617 PET/CT before and one month after the treatment. Dosimetry evaluation was compared in both patient groups.


When the bone metastasis tumors with comparable baseline SUVmax in the range of 10.0–15.0 were selected from the two groups for comparison, the accumulated radioactivity of 177Lu-EB-PSMA-617 was about 3.02-fold higher than that of 177Lu-PSMA-617. Imaging dose of 177Lu-EB-PSMA-617 treatment showed significant decrease of 68Ga-PSMA-617 uptake within a month, which was not observed in patients imaged with 177Lu-PSMA-617 (SUV change: −32.43 ± 0.14% vs. 0.21 ± 0.37%; P = 0.002). 177Lu-EB-PSMA-617 also had higher absorbed doses in the red bone marrow and kidneys than 177Lu-PSMA-617 (0.0547 ± 0.0062 vs. 0.0084 ± 0.0057 mSv/MBq for red bone marrow, P < 0.01; 2.39 ± 0.69 vs. 0.39 ± 0.06 mSv/MBq for kidneys, P < 0.01).


This first-in-human study demonstrated that 177Lu-EB-PSMA-617 had higher accumulation in mCRPC and that low imaging dose appears to be effective in treating tumors with high 68Ga-PSMA-617 uptakes. Elevated uptakes of 177Lu-EB-PSMA-617 in kidneys and red bone marrow were well tolerated at the administered low dose. Further investigations with increased dose and frequency of administration are warranted.


Radioligand therapy (RLT) 177Lu Evans blue Prostate-specific membrane antigen (PSMA) Metastatic castration-resistant prostate cancer (mCRPC) 



This study was supported in part by the Key Project on Inter-Governmental International Scientific and Technological Innovation Cooperation in National Key Projects of Research and Development Plan (2016YFE0115400), the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), and National Institutes of Health (NIH). This study was also partly supported by the Chinese Academy of Medical Science Major Collaborative Innovation Project (2016-I2M-1-011), Welfare Research Funding for Public Health Professionals (201402001), National Nature Science Foundation (81741142) and Beijing Municipal Natural Science Foundation (7161012).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Nuclear Medicine, Peking Union Medical College (PUMC) HospitalChinese Academy of Medical Science and PUMCBeijingChina
  2. 2.Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear MedicineBeijingChina
  3. 3.Department of Urology, Peking Union Medical College (PUMC) HospitalChinese Academy of Medical Science and PUMCBeijingChina
  4. 4.Laboratory of Molecular Imaging and Nanomedicine (LOMIN)National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)BethesdaUSA

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