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. 2019 Jan;46(1):148-158.
doi: 10.1007/s00259-018-4096-y. Epub 2018 Aug 8.

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

Jie Zang  1   2 , Xinrong Fan  3 , Hao Wang  1   2 , Qingxing Liu  1   2 , Jingnan Wang  1   2 , Hui Li  1   2 , Fang Li  1   2 , Orit Jacobson  4 , Gang Niu  4 , Zhaohui Zhu  5   6   7 , Xiaoyuan Chen  8
Affiliations

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

Jie Zang et al. Eur J Nucl Med Mol Imaging. 2019 Jan.

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

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

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Conflict of interest statement

Compliance with Ethical Standards

Conflict of Interest: The authors declare that declares they have no conflict of interest.

Figures

FIGURE 1.
FIGURE 1.
(A) Representative whole-body anterior projection images of a 70-y-old male patient with mCRPC at different time points after intravenous administration of 177Lu-EB-PSMA-617. (B) Representative whole-body anterior projection images of a 72-y-old male patient with mCRPC at different time points after intravenous administration of 177Lu-PSMA-617.
FIGURE 2.
FIGURE 2.
Time-activity curves and number of disintegrations of all the lesions (A, B), all the bone lesions (C, D) and the bone tumors with comparable baseline SUVmax of 68Ga-PSMA-617 activity from 10.0–15.0 after administration of 177Lu-EB-PSMA-617 (red) and 177Lu-PSMA-617 (blue).
FIGURE 3.
FIGURE 3.
Comparison of 68Ga-PSMA-617 PET/CT images immediately before (A) and 1 month after (B) injection of 1.11 GBq (30.0 mCi) of 177Lu-EB-PSMA-617 in a patient (patient 1) with mCRPC. The SUVmax of the right scapula decreased from 10 to 3 (red arrow), and the SUVmax of bone metastasis in T6 decreased from 21 to 7 (blue arrow). Comparison of 68Ga-PSMA-617 PET/CT images immediately before (C) and 1 month after (D) injection of 1.27GBq (34.30 mCi) of 177Lu-PSMA-617 in a patient (patient 7) with mCRPC. The SUVmax of bone metastasis in S1 increased from 5 to 12 (green arrow), and the SUVmax of the right ilium increased from 4 to 8 (yellow arrow).
See this image and copyright information in PMC

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