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 highGa-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.

This study was designed to analyze the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR) antagonist PET tracer, Ga-RM26; to assess its clinical diagnostic value in prostate cancer patients; and to perform a direct comparison between GRPR antagonist Ga-RM26 and agonistGa-BBN. Five healthy volunteers were enrolled to validate the safety ofGa-RM26 and calculate dosimetry. A total of 28 patients with prostate cancer (17 newly diagnosed and 11 posttherapy) were recruited and provided written informed consent. All the cancer patients underwent PET/CT at 15-30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of Ga-RM26. Among them, 22 patients (11 newly diagnosed and 11 posttherapy) underwentGa-BBN PET/CT for comparison within 1 wk. Tc-MDP (methylene diphosphonate) bone scans were obtained within 2 wk for comparison. GRPR immunohistochemical staining of tumor samples was performed. The administration of Ga-M26 was well tolerated by all subjects, with no adverse symptoms being noticed or reported during the procedure and at 2-wk follow-up. The total effective dose equivalent and effective dose were 0.0912 ± 0.0140 and 0.0657 ± 0.0124 mSv/MBq, respectively. In the 17 patients with newly diagnosed prostate cancer,Ga-RM26 PET/CT showed positive prostate-confined findings in 15 tumors with an SUV of 6.49 ± 2.37. In the 11 patients who underwent prostatectomy or brachytherapy with or without androgen deprivation therapy, Ga-RM26 PET/CT detected 8 metastatic lymph nodes in 3 patients with an SUV of 4.28 ± 1.25 and 21 bone lesions in 8 patients with an SUV of 3.90 ± 3.07. Compared with Ga-RM26 PET/CT, GRPR agonistGa-BBN PET/CT detected fewer primary lesions and lymph node metastases as well as demonstrated lower tracer accumulation. There was a significant positive correlation between SUV derived from Ga-RM26 PET and the expression level of GRPR ( < 0.001). This study indicates the safety and significant efficiency of GRPR antagonistGa-RM26. Ga-RM26 PET/CT would have remarkable value in detecting both primary prostate cancer and metastasis.Ga-RM26 is also expected to be better than GRPR agonist as an imaging marker to evaluate GRPR expression in prostate cancer.