Teli Liu1, Chen Liu1, Zhongyi Zhang2, Ning Zhang3, Xiaoyi Guo1, Lei Xia1, Jinquan Jiang1, Qing Xie1, Kun Yan2, Steven P Rowe4, Hua Zhu5, Zhi Yang6. 1. Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Rd, Beijing, 100142, China. 2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasonography, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Rd, Beijing, 100142, China. 3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Urology, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Rd, Beijing, 100142, China. 4. The James Buchanan Brady Urology Institute and Department of Urology, and The Russell H. Morgan, Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 N. Caroline St., Rm. 3233, Baltimore, MD, 21287, USA. srowe8@jhmi.edu. 5. Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Rd, Beijing, 100142, China. zhuhuananjing@163.com. 6. Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Rd, Beijing, 100142, China. pekyz@163.com.
Abstract
PURPOSE: Develop a 64Cu labeled radiopharmaceutical targeting prostate specific membrane antigen (PSMA) and investigate its application for prostate cancer imaging. METHODS: 64Cu-PSMA-BCH was prepared and investigated for stability, PSMA specificity, and micro-PET imaging. With the approval of Ethics Committee of Beijing Cancer Hospital (No. 2017KT97), PET/CT imaging in 4 patients with suspected prostate cancer was performed and the radiation dosimetry was estimated. Then, PSMA PET-ultrasound image-guided biopsies were performed on 3 patients and the fine needle aspirates were further performed for autoradiography and immunohistochemistry analysis. RESULTS: 64Cu-PSMA-BCH was prepared with high radiochemical yield and stability. In vivo study showed higher uptake in PSMA ( +) 22Rv1 cells than PSMA ( -) PC-3 cells (5.59 ± 0.36 and 1.97 ± 0.22 IA%/106 cells at 1 h). It accumulated in 22Rv1 tumor with increasing radioactivity uptake and T/N ratios from 1 to 24 h post-injection. In patients with suspected prostate cancer, SUVmax and T/N ratios increased within 24 h post-injection. Compared with image at 1 h post-injection, more tumor lesions were detected at 6 h and 24 h post-injection. The human organ radiation dosimetry showed gallbladder wall was most critical, liver and kidneys were followed, and the whole-body effective dose was 0.0292 mSv/MBq. Two fine needle aspirates obtained by PET-ultrasound-guided targeted biopsy showed high radioactive signal by autoradiography, with 100% PSMA expression in cytoplasm and 30% expression in nucleus. CONCLUSION: 64Cu-PSMA-BCH was PSMA specific and showed high stability in vivo with lower uptake in liver than 64Cu-PSMA-617. Biodistribution in mice and PCa patients showed similar profile compared with other PSMA ligands and it was safe with moderate effective dosimetry. The increased tumor uptake and T/N ratios by delayed imaging may facilitate the detection of small lesions and guiding targeted biopsies.
PURPOSE: Develop a 64Cu labeled radiopharmaceutical targeting prostate specific membrane antigen (PSMA) and investigate its application for prostate cancer imaging. METHODS:64Cu-PSMA-BCH was prepared and investigated for stability, PSMA specificity, and micro-PET imaging. With the approval of Ethics Committee of Beijing Cancer Hospital (No. 2017KT97), PET/CT imaging in 4 patients with suspected prostate cancer was performed and the radiation dosimetry was estimated. Then, PSMA PET-ultrasound image-guided biopsies were performed on 3 patients and the fine needle aspirates were further performed for autoradiography and immunohistochemistry analysis. RESULTS:64Cu-PSMA-BCH was prepared with high radiochemical yield and stability. In vivo study showed higher uptake in PSMA ( +) 22Rv1 cells than PSMA ( -) PC-3 cells (5.59 ± 0.36 and 1.97 ± 0.22 IA%/106 cells at 1 h). It accumulated in 22Rv1tumor with increasing radioactivity uptake and T/N ratios from 1 to 24 h post-injection. In patients with suspected prostate cancer, SUVmax and T/N ratios increased within 24 h post-injection. Compared with image at 1 h post-injection, more tumor lesions were detected at 6 h and 24 h post-injection. The human organ radiation dosimetry showed gallbladder wall was most critical, liver and kidneys were followed, and the whole-body effective dose was 0.0292 mSv/MBq. Two fine needle aspirates obtained by PET-ultrasound-guided targeted biopsy showed high radioactive signal by autoradiography, with 100% PSMA expression in cytoplasm and 30% expression in nucleus. CONCLUSION:64Cu-PSMA-BCH was PSMA specific and showed high stability in vivo with lower uptake in liver than 64Cu-PSMA-617. Biodistribution in mice and PCa patients showed similar profile compared with other PSMA ligands and it was safe with moderate effective dosimetry. The increased tumor uptake and T/N ratios by delayed imaging may facilitate the detection of small lesions and guiding targeted biopsies.
Authors: Chen Liu; Teli Liu; Zhongyi Zhang; Ning Zhang; Peng Du; Yong Yang; Yiqiang Liu; Wei Yu; Nan Li; Michael A Gorin; Steven P Rowe; Hua Zhu; Kun Yan; Zhi Yang Journal: J Nucl Med Date: 2020-02-07 Impact factor: 10.057
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