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In vitro and in vivo comparative study of 68Ga-labeled DOTA-, NOTA-, and HBEDCC-chelated radiotracers targeting prostate-specific membrane antigen

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Abstract

68Ga-radiolabeled small molecules targeting prostate-specific membrane antigen (PSMA) have been extensively investigated as 68Ga-positron emission tomography (68Ga-PET) tracers. Nevertheless, current 68Ga-labeled radiotracers suffer from either fair detection rates for metastatic prostate cancer lesions or a high uptake by the kidneys. This study synthesizes new PSMA-targeted radiotracers, [68Ga]SC691-DOTA, [68Ga]SC691-NOTA, and [68Ga]SC691-HBEDCC, and explores the in vitro and in vivo properties. These three radiotracers enabled PSMA-positive LNCaP tumors to be visualized by micro-PET/CT as early as 5 min post-injection. Biodistribution studies revealed that all three compounds could accumulate in the tumor with high affinity. The kidney’s uptake of [68Ga]SC691-DOTA and [68Ga]SC691-NOTA was comparable but lower than [68Ga]SC691-HBEDCC. [68Ga]SC691-HBEDCC demonstrated the most increased uptake and retention in the tumor over 2 h post-injection and a lower tumor-to-tissue ratio than [68Ga]SC691-DOTA, and [68Ga]SC691-NOTA.

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Acknowledgements

The authors would like to thank the National Natural Science Foundation of China for funding this work (U20A20384); the Doctoral Research Initiation Fund of Affiliated Hospital of Southwest Medical University; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province (HYX19001), the Sichuan Science and Technology Foundation (2021YJ0131 and 2020ZYD101), and Luzhou-Southwest Medical University Cooperative Application Foundation (2020LZXNYDJ50)

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Authors and Affiliations

  1. The Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou, Sichuan, China

    Yang Liu, Li Xia, Ping Cai, Yingwen Wang, Yue Feng, Yue Chen & Zhijun Zhou

  2. Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Jiangyang District, Luzhou, Sichuan, China

    Yang Liu, Li Xia, Ping Cai, Yingwen Wang, Yue Feng, Yue Chen & Zhijun Zhou

  3. Academician (Expert) Workstation of Sichuan Province, Jiangyang District, Luzhou, Sichuan, China

    Yang Liu, Yue Feng, Yue Chen & Zhijun Zhou

  4. Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Jiangyang District, Luzhou, Sichuan, China

    Li Xia, Ping Cai, Yingwen Wang & Zhijun Zhou

  5. Department of Nuclear Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China

    Wei Zhang & Nan Liu

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Contributions

Conceptualization: ZZ. Methodology: ZZ, NL, YL. Validation: YL, LX. Formal analysis: ZZ, YL. Investigation: YL, LX, PC, YW, YF, WZ. Resources: YC, WZ. Data curation: YL, LX. Writing: ZZ. Funding acquisition: YC, ZZ, WZ. Review: ZZ, YL, LX, PC, YW, YF, WZ, YC, NL.

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Correspondence to Nan Liu, Yue Chen or Zhijun Zhou.

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Institutional Review Board Statement: The Ethics Committee for Southwest Medical University (2021-02-29) approved the study. All methods were carried out following relevant guidelines and regulations, and all methods are reported per ARRIVE guidelines.

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Liu, Y., Xia, L., Cai, P. et al. In vitro and in vivo comparative study of 68Ga-labeled DOTA-, NOTA-, and HBEDCC-chelated radiotracers targeting prostate-specific membrane antigen. J Radioanal Nucl Chem 332, 617–628 (2023). https://doi.org/10.1007/s10967-022-08731-1

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