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[177Lu]Lu-PSMA-617 theranostic probe for hepatocellular carcinoma imaging and therapy

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Abstract

Purpose

This study aimed to explore the feasibility of using [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 and [177Lu]Lu-Evans blue (EB)-PSMA-617 for in vivo radioligand therapy by single-dose administration in a PSMA-positive hepatocellular carcinoma (HCC) xenograft mouse model.

Methods

[177Lu]Lu-PSMA-617 and [177Lu]Lu-EB-PSMA-617 were prepared, and labelling efficiency and radiochemical purity were determined. A HepG2 human HCC subcutaneous xenograft mouse model was established. After intravenous injection of [177Lu]Lu-PSMA-617 or [177Lu]Lu-EB-PSMA-617 (37 MBq) into the mouse model, single-photon emission computed tomography/computed tomography (SPECT/CT) was performed. Biodistribution studies were conducted to verify targeting specificity and pharmacokinetics. In the radioligand therapy study, mice were randomized into 4 groups: 37 MBq [177Lu]Lu-PSMA-617, 18.5 MBq [177Lu]Lu-PSMA-617, 7.4 MBq [177Lu]Lu-EB-PSMA-617, and saline (control). A single-dose administration was applied at the beginning of therapy studies. Tumor volume, body weight, and survival were monitored every 2 days. After the end of therapy, mice were euthanized. Tumors were then weighed, and systemic toxicity was evaluated via blood testing and histological examination of healthy organs.

Results

[177Lu]Lu-PSMA-617 and [177Lu]Lu-EB-PSMA-617 were successfully prepared with high purity and stability. SPECT/CT and biodistribution showed that tumor uptake was higher and persisted longer for [177Lu]Lu-EB-PSMA-617 compared with [177Lu]Lu-PSMA-617. [177Lu]Lu-PSMA-617 was rapidly cleared from the blood, while [177Lu]Lu-EB-PSMA-617 persisted for significantly longer. In radioligand therapy studies, tumor growth was significantly suppressed in the 37 MBq [177Lu]Lu-PSMA-617, 18.5 MBq [177Lu]Lu-PSMA-617, and 7.4 MBq [177Lu]Lu-EB-PSMA-617 groups compared to the saline group. Median survival was 40, 44, 43, and 30 days, respectively. No healthy organ toxicity was observed in safety and tolerability evaluation.

Conclusions

Radioligand therapy using [177Lu]Lu-PSMA-617 and [177Lu]Lu-EB-PSMA-617 significantly suppressed tumor growth and prolonged survival time in PSMA-positive HCC xenograft mice without obvious toxicity. These radioligands appear promising for clinical use in humans, and future studies are warranted.

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Data Availability

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary information.

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Acknowledgements

We would like to acknowledge the service provided by Beijing Novel Medical Equipment Ltd. for image acquisition. We thank Liwen Bianji (Edanz) (https://www.liwenbianji.cn) for editing the language of a draft of this manuscript.

Funding

This work was funded by the National Natural Science Foundation of China (No. 82030052).

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Authors and Affiliations

  1. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China

    Qiaomiao Lu, Yu Long, Yongkang Gai, Qingyao Liu, Dawei Jiang & Xiaoli Lan

  2. Hubei Key Laboratory of Molecular Imaging, Wuhan, Hubei, 430022, China

    Qiaomiao Lu, Yu Long, Yongkang Gai, Qingyao Liu, Dawei Jiang & Xiaoli Lan

  3. Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan, 430022, China

    Yongkang Gai, Qingyao Liu, Dawei Jiang & Xiaoli Lan

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  1. Qiaomiao Lu
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Correspondence to Xiaoli Lan.

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All experimental schemes were performed under the guidance and approved by the Institutional Animal Care and Use Committee of Tongji Medical College of Huazhong University of Science and Technology ([2021] IACUC Number: 2688). Extensive efforts were made to ensure minimal suffering of the animals used during the study.

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Lu, Q., Long, Y., Gai, Y. et al. [177Lu]Lu-PSMA-617 theranostic probe for hepatocellular carcinoma imaging and therapy. Eur J Nucl Med Mol Imaging 50, 2342–2352 (2023). https://doi.org/10.1007/s00259-023-06155-x

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