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Automatic radiosynthesis and preclinical evaluation of 18F-AlF-PSMA-NF as a potential PET probe for prostate cancer imaging

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Abstract

Facile automatic production is important for the application of prostate-specific membrane antigen (PSMA) tracers in clinical practice. We developed a new 18F-AlF-labelled PSMA probe—18F-AlF-PSMA-NF—and explore its automated production method and potential value in clinical settings. 18F-AlF-PSMA-NF was prepared using an automated method with dimethylformamide (DMF) as the solvent in a positron emission tomography (PET)-MF-2 V-IT-I synthesizer. Tracer characteristics were examined both in vitro and in vivo. Micro-PET/computed tomography (CT) was performed to investigate the utility of 18F-AlF-PSMA-NF for imaging PSMA-positive tumours in vivo. 18F-AlF-PSMA-NF was prepared automatically within 35 min with a non-attenuation correction yield of 37.9 ± 11.2%. The tracer was hydrophilic, had a high affinity for PSMA (Kd = 2.58 ± 0.81 nM), and showed stability in both in vitro and in vivo conditions. In the cellular experiments, 18F-AlF-PSMA-NF uptake in PSMA-positive LNCaP cells was significantly higher than that in PSMA-negative PC-3 cells (P < 0.001), and could be blocked by excess ZJ-43—a PSMA inhibitor (P < 0.001). LNCaP tumours were clearly visualized by 18F-AlF-PSMA-NF on micro-PET/CT, with a high level of uptake (13.72 ± 2.01 percent injected dose per gram of tissue [%ID/g]) and high tumour/muscle ratio (close to 50:1). The PSMA-positive LNCaP tumours had a significantly higher uptake than PSMA-negative PC-3 tumours (13.72 ± 2.01%ID/g vs. 1.07 ± 0.48%ID/g, t = 10.382, P < 0.001), and could be blocked by ZJ-43 (13.72 ± 2.01%ID/g vs. 2.77 ± 1.44%ID/g, t = 8.14, P < 0.001). A new 18F-AlF-labelled PSMA probe—18F-AlF-PSMA-NF—was successfully developed and can be prepared automatically. It has the biological characteristics resembling that of a PSMA-based probe and can potentially be used in clinical settings.

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Availability of data and material

The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the National Natural Science Foundation Project of China (81873905, 81901781).

Funding

This work was supported by the National Natural Science Foundation Project of China (81873905, 81901781).

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Author notes

  1. Wenlan Zhou and Shun Huang contributed equally to this work.

Authors and Affiliations

  1. Department of NanFang PET Center, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong Province, China

    Wenlan Zhou, Shun Huang, Yanping Jiang, Kongzhen Hu, Lijuan Wang, Yanjiang Han & Hubing Wu

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  1. Wenlan Zhou
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  2. Shun Huang
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  3. Yanping Jiang
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  4. Kongzhen Hu
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  5. Lijuan Wang
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  7. Hubing Wu
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Contributions

Initials: Wenlan Zhou (WLZ), Shun Huang (SH), Yanping Jiang (YPJ), Kongzhen Hu (KZH), Lijuan Wang (LJW), Yanjiang Han (HYJ), Hubing Wu (HBW). Conceived and designed the study: WLZ, SH, KZH, and HBW. Performed the experiment: WLZ, SH, YPJ, and LJW. Performed the data analyses: WLZ, SH, and HBW. Administrative, technical, or material support: YPJ, HYJ, and LJW. Writing, review, and/or revision of the manuscript: all authors. All authors read and approved the manuscript. Wenlan Zhou and Shun Huang contributed equally to this work.

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Correspondence to Hubing Wu.

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This article does not contain any studies with human participants. All animal studies were performed according to a protocol approved by the Southern Medical University Nanfang Hospital Animal Care and Use Committee.

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Communicated by J. Pietzsch.

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Zhou, W., Huang, S., Jiang, Y. et al. Automatic radiosynthesis and preclinical evaluation of 18F-AlF-PSMA-NF as a potential PET probe for prostate cancer imaging. Amino Acids 53, 929–938 (2021). https://doi.org/10.1007/s00726-021-02997-7

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