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64Cu-PSMA-BCH: a new radiotracer for delayed PET imaging of prostate cancer

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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Funding

This study was fund by Beijing Natural Science Foundation (Nos. 7194246, 7202028), Science Foundation of Peking University Cancer Hospital 2020–17, Beijing Excellent Talents Funding (2017000021223ZK33), Beijing Millions of Talents Projects A level funding (No. 2019A38), and Municipal Administration of Hospitals-Yangfan Project (ZYLX201816).

Author information

Author notes

  1. Teli Liu, Chen Liu and Zhongyi Zhang contributed equally to this work.

Authors and Affiliations

  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

    Teli Liu, Chen Liu, Xiaoyi Guo, Lei Xia, Jinquan Jiang, Qing Xie, Hua Zhu & Zhi Yang

  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

    Zhongyi Zhang & Kun Yan

  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

    Ning Zhang

  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

    Steven P. Rowe

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  1. Teli Liu
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Corresponding authors

Correspondence to Steven P. Rowe, Hua Zhu or Zhi Yang.

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Ethical approval

All animal experiments were conducted in accordance with the guidelines approved by Peking University Cancer Hospital Animal Care and Use Committee. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by Ethics Committee of Beijing Cancer Hospital and Institute (No.2017KT97).

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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This article is part of the Topical Collection on Radiopharmacy

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Liu, T., Liu, C., Zhang, Z. et al. 64Cu-PSMA-BCH: a new radiotracer for delayed PET imaging of prostate cancer. Eur J Nucl Med Mol Imaging 48, 4508–4516 (2021). https://doi.org/10.1007/s00259-021-05426-9

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