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

PURPOSE

This translational study is designed to assess the safety, dosimetry and therapeutic response to a single, low-dose of Lu-EB-PSMA-617 in comparison to Lu-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 Lu-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) Lu-PSMA-617, then underwent the same imaging procedures at 0.5, 2, 24, 48, and 72 h. All patients were evaluated by Ga-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 SUV in the range of 10.0-15.0 were selected from the two groups for comparison, the accumulated radioactivity of Lu-EB-PSMA-617 was about 3.02-fold higher than that of Lu-PSMA-617. Imaging dose of Lu-EB-PSMA-617 treatment showed significant decrease of Ga-PSMA-617 uptake within a month, which was not observed in patients imaged with Lu-PSMA-617 (SUV change: -32.43 ± 0.14% vs. 0.21 ± 0.37%; P = 0.002). Lu-EB-PSMA-617 also had higher absorbed doses in the red bone marrow and kidneys than Lu-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 Lu-EB-PSMA-617 had higher accumulation in mCRPC and that low imaging dose appears to be effective in treating tumors with high Ga-PSMA-617 uptakes. Elevated uptakes of Lu-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.