Jingjing Zhang1,2,3, Gang Niu3, Xinrong Fan4, Lixin Lang3, Guozhu Hou1,2, Libo Chen5,2, Huanwen Wu6, Zhaohui Zhu5,2, Fang Li1,2, Xiaoyuan Chen7. 1. Department of Nuclear Medicine, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Science & PUMC, Beijing, China. 2. Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China. 3. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland. 4. Department of Urology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Science & PUMC, Beijing, China; and. 5. Department of Nuclear Medicine, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Science & PUMC, Beijing, China 13611093752@163.com shawn.chen@nih.gov. 6. Department of Pathology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Science & PUMC, Beijing, China. 7. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 13611093752@163.com shawn.chen@nih.gov.
Abstract
This study was designed to analyze the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR) antagonist PET tracer, 68Ga-RM26; to assess its clinical diagnostic value in prostate cancer patients; and to perform a direct comparison between GRPR antagonist 68Ga-RM26 and agonist 68Ga-BBN. Methods: Five healthy volunteers were enrolled to validate the safety of 68Ga-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 68Ga-RM26. Among them, 22 patients (11 newly diagnosed and 11 posttherapy) underwent 68Ga-BBN PET/CT for comparison within 1 wk. 99mTc-MDP (methylene diphosphonate) bone scans were obtained within 2 wk for comparison. GRPR immunohistochemical staining of tumor samples was performed. Results: The administration of 68Ga-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, 68Ga-RM26 PET/CT showed positive prostate-confined findings in 15 tumors with an SUVmax of 6.49 ± 2.37. In the 11 patients who underwent prostatectomy or brachytherapy with or without androgen deprivation therapy, 68Ga-RM26 PET/CT detected 8 metastatic lymph nodes in 3 patients with an SUVmax of 4.28 ± 1.25 and 21 bone lesions in 8 patients with an SUVmax of 3.90 ± 3.07. Compared with 68Ga-RM26 PET/CT, GRPR agonist 68Ga-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 68Ga-RM26 PET and the expression level of GRPR (P < 0.001). Conclusion: This study indicates the safety and significant efficiency of GRPR antagonist 68Ga-RM26. 68Ga-RM26 PET/CT would have remarkable value in detecting both primary prostate cancer and metastasis. 68Ga-RM26 is also expected to be better than GRPR agonist as an imaging marker to evaluate GRPR expression in prostate cancer.
This study was designed to analyze the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR) antagonist PET tracer, 68Ga-RM26; to assess its clinical diagnostic value in prostate cancerpatients; and to perform a direct comparison between GRPR antagonist 68Ga-RM26 and agonist 68Ga-BBN. Methods: Five healthy volunteers were enrolled to validate the safety of 68Ga-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 cancerpatients underwent PET/CT at 15-30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of 68Ga-RM26. Among them, 22 patients (11 newly diagnosed and 11 posttherapy) underwent 68Ga-BBN PET/CT for comparison within 1 wk. 99mTc-MDP (methylene diphosphonate) bone scans were obtained within 2 wk for comparison. GRPR immunohistochemical staining of tumor samples was performed. Results: The administration of 68Ga-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, 68Ga-RM26 PET/CT showed positive prostate-confined findings in 15 tumors with an SUVmax of 6.49 ± 2.37. In the 11 patients who underwent prostatectomy or brachytherapy with or without androgen deprivation therapy, 68Ga-RM26 PET/CT detected 8 metastatic lymph nodes in 3 patients with an SUVmax of 4.28 ± 1.25 and 21 bone lesions in 8 patients with an SUVmax of 3.90 ± 3.07. Compared with 68Ga-RM26 PET/CT, GRPR agonist 68Ga-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 68Ga-RM26 PET and the expression level of GRPR (P < 0.001). Conclusion: This study indicates the safety and significant efficiency of GRPR antagonist 68Ga-RM26. 68Ga-RM26 PET/CT would have remarkable value in detecting both primary prostate cancer and metastasis. 68Ga-RM26 is also expected to be better than GRPR agonist as an imaging marker to evaluate GRPR expression in prostate cancer.
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