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

Teli Liu; Chen Liu; Zhongyi Zhang; Ning Zhang; Xiaoyi Guo; Lei Xia; Jinquan Jiang; Qing Xie; Kun Yan; Steven P. Rowe; Hua Zhu; Zhi Yang

doi:10.1007/s00259-021-05426-9

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

Teli Liu, Chen Liu, Zhongyi Zhang, Ning Zhang, Xiaoyi Guo, Lei Xia, Jinquan Jiang, Qing Xie, Kun Yan, Steven P. Rowe, Hua Zhu, Zhi Yang

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	4508-4516
Number of pages	9
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	48
Issue number	13
DOIs	https://doi.org/10.1007/s00259-021-05426-9
State	Published - Dec 2021

Keywords

Cu-PSMA
Delayed imaging
PET/CT
Prostate cancer
Targeted biopsies

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

Access to Document

10.1007/s00259-021-05426-9

Cite this

@article{b6bb06d3734a4e5bb7907a869692a3f8,

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

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.",

keywords = "Cu-PSMA, Delayed imaging, PET/CT, Prostate cancer, Targeted biopsies",

author = "Teli Liu and Chen Liu and Zhongyi Zhang and Ning Zhang and Xiaoyi Guo and Lei Xia and Jinquan Jiang and Qing Xie and Kun Yan and Rowe, {Steven P.} and Hua Zhu and Zhi Yang",

note = "Funding Information: 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). Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2021",

month = dec,

doi = "10.1007/s00259-021-05426-9",

language = "English (US)",

volume = "48",

pages = "4508--4516",

journal = "European Journal of Nuclear Medicine and Molecular Imaging",

issn = "1619-7070",

publisher = "Springer Verlag",

number = "13",

}

TY - JOUR

T1 - 64Cu-PSMA-BCH

T2 - a new radiotracer for delayed PET imaging of prostate cancer

AU - Liu, Teli

AU - Liu, Chen

AU - Zhang, Zhongyi

AU - Zhang, Ning

AU - Guo, Xiaoyi

AU - Xia, Lei

AU - Jiang, Jinquan

AU - Xie, Qing

AU - Yan, Kun

AU - Rowe, Steven P.

AU - Zhu, Hua

AU - Yang, Zhi

N1 - Funding Information: 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). Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

KW - Cu-PSMA

KW - Delayed imaging

KW - PET/CT

KW - Prostate cancer

KW - Targeted biopsies

UR - http://www.scopus.com/inward/record.url?scp=85108792845&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85108792845&partnerID=8YFLogxK

U2 - 10.1007/s00259-021-05426-9

DO - 10.1007/s00259-021-05426-9

M3 - Article

C2 - 34170361

AN - SCOPUS:85108792845

SN - 1619-7070

VL - 48

SP - 4508

EP - 4516

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

IS - 13

ER -