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Ankylosing spondylitis PET imaging and quantifications via P2X7 receptor-targeting radioligand [18F]GSK1482160

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Abstract

Purpose

Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial spine; however, the quantitative detection of inflammation in AS remains a challenge in clinical settings. We aimed to investigate the feasibility of using a specific P2X7R-targeting 18F-labeled tracer [18F]GSK1482160 for positron emission tomography (PET) imaging and the quantification of AS.

Methods

The radioligand [18F]GSK1482160 was obtained based on nucleophilic aliphatic substitution. Dynamic [18F]GSK1482160 and [18F]FDG micro-PET/CT imaging were performed on AS mice (n = 8) and age-matched controls (n = 8). Tracer kinetics modeling was performed using Logan’s graphical arterial input function analysis to quantify the in vivo expression of P2X7R. The post-PET tissues were collected for hematoxylin–eosin (H&E), immunohistochemical (IHC), and immunofluorescence (IF) staining.

Results

[18F]GSK1482160 PET/CT imaging revealed that the specific binding in the ankle joint and sacroiliac joint (SIJ) of the AS at 8 weeks group (BPNDankle−AS−8W (non-displaceable binding potential of the ankle) 3.931 ± 0.74; BPND SIJ−AS−8W (BPBD of the SIJ) 4.225 ± 0.84) were significantly higher than the controls at 8 weeks group (BPNDankle−Ctr−8W 0.325 ± 0.15, BPNDSJJ−Ctr−8W 0.319 ± 0.17) respectively, and the AS at 14 weeks group (BPNDankle−AS−14W 12.212 ± 2.25; BPNDSJJ−AS−14W 13.389 ± 3.60) were significantly higher than the controls at 14 weeks group (BPNDankle−Ctr−14W 0.204 ± 0.16, BPNDSJJ−Ctr−14W 0.655 ± 0.35) respectively. The four groups had no significant difference in the [18F]FDG uptake of ankle and SIJ. IHC and IF staining revealed that the overexpression of P2X7R was colocalized with activated macrophages from the ankle synovium and spinal endplate in mice with AS, indicating that quantification of P2X7R may contribute to the understanding of the pathogenesis of inflammation in human AS.

Conclusion

This study developed a novel P2X7R-targeting PET tracer [18F]GSK1482160 to detect the expression of P2X7R in AS mouse models and provided powerful non-invasive PET imaging and quantification for AS.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank Dr. Chunlei Han (Turku PET center, Finland) and Min Yang for technique supports for the tracer kinetics modeling.

Funding

This work was supported by National Natural Science Foundation of China (81871382, 82150610508,12126603), the Key Realm R&D Program of Guangdong Province (2018B030337001), the Guangdong Provincial Basic and Applied Basic Research Fund Provincial Enterprise Joint Fund (2021A1515220004), Guangdong-Macao Science and Technology Innovation Joint Funding Project (0056/2021/AGJ), Zhuhai City Innovation and Innovation Team Project (ZH0406190031PWC), and Zhuhai City Industry-University-Research Cooperation Project (ZH22017002210017PWC).

Author information

Author notes

  1. Shiyanjin Zhang, Yifan Qiu and Lihua Huang equally contributed to this work.

Authors and Affiliations

  1. Department of Spine Surgery, Sun Yat-Sen University Fifth Affiliated Hospital, Zhuhai, 519000, Guangdong Province, China

    Shiyanjin Zhang, Lihua Huang, Yuanqing Guo, Ke You, Yuhan Wang & Hai Lu

  2. Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong Province, China

    Yifan Qiu, Lihua Huang, Lei Bi, Guolong Huang, Hongjun Jin & Hong Shan

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  1. Shiyanjin Zhang
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Contributions

Zhang S., Qiu Y., and Huang L. contributed equally to this work. Jin H. and Lu H. conceived and designed the experiments. Qiu Y. radio-synthesized and Huang G. characterized the agents. Zhang S., Huang L., Bi L., and Huang G. performed the PET/CT for rodents studies. Zhang S. and Huang L. performed the AS modeling, biological scoring, H&E, and immunofluorescence. You K., Guo Y., and Lu H. collected clinical specimens. Zhang S., Huang L., and Jin H. analyzed the PET imaging data. Jin H., Lu H, and Zhang S. co-wrote the paper. Shan H. and Wang Y. provided constructive discussion. All authors discussed the results and analysis and commented on the manuscript.

Corresponding authors

Correspondence to Hai Lu or Hongjun Jin.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of FAHSYSU (No. 2019051701 and No. ZDWY. JZWK. 002).

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

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The authors affirm that human research participants provided informed consent for the publication of the images in Fig. 7a and b.

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All authors have no relevant financial or non-financial interests to disclose.

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Zhang, S., Qiu, Y., Huang, L. et al. Ankylosing spondylitis PET imaging and quantifications via P2X7 receptor-targeting radioligand [18F]GSK1482160. Eur J Nucl Med Mol Imaging 50, 3589–3601 (2023). https://doi.org/10.1007/s00259-023-06342-w

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