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Purpose <p>Elevated Stabilin-2 (STAB2) expression in macrophages within atherosclerotic plaques offers a promising molecular target for imaging vascular inflammation. The S2P peptide specifically binds STAB2. This study aims to evaluate the feasibility of using the STAB2-targeted <sup>18</sup>F-labeled tracer (<sup>18</sup>F-S2P) for positron emission tomography (PET) imaging to identify atherosclerotic plaques.</p> Methods <p><i>Stab2 </i>expression was validated via single-cell RNA sequencing of <i>Ldlr</i><sup>−/−</sup> mouse samples. Biodistribution and micro-PET/CT imaging were performed in high-fat diet-fed <i>Ldlr</i><sup>−/−</sup> mice (3–12 weeks) and chow-fed controls, with comparisons to <sup>18</sup>F-FDG and <sup>18</sup>F-Pentixafor. Plaque burden and macrophage infiltration were evaluated using Oil Red O, H&amp;E, and immunofluorescence staining. Immunohistochemical staining was used to detect STAB2 expression in human atherosclerotic specimens.</p> Results <p>ScRNA-seq analysis identified <i>Stab2</i> as a macrophage-specific marker in atherosclerosis plaque. In vivo micro-PET/CT quantification revealed disease duration-dependent uptake (1.41 ± 0.31 ID%/g at 3 weeks vs. 2.17 ± 0.19 ID%/g at 12 weeks, <i>P</i> &lt; 0.0001), which positively correlated with histological plaque burden. <sup>18</sup>F-S2P PET imaging demonstrated 5.4-fold higher plaque uptake in <i>Ldlr</i><sup><i>−/−</i></sup> mice compared to wild-type controls (<i>P</i> &lt; 0.0001), significantly outperforming <sup>18</sup>F-FDG (1.52-fold) and <sup>18</sup>F-Pentixafor (1.89-fold) in atherosclerotic lesions. Furthermore, STAB2 was also detectable in human atherosclerotic plaques.</p> Conclusion <p>This study introduces a novel STAB2-targeted PET probe (<sup>18</sup>F-S2P) for non-invasive imaging of atherosclerotic plaques in preclinical models, enabling the detection of atherosclerotic inflammation. The endogenous expression of STAB2 in human atherosclerotic lesions further strengthens the translational potential of this imaging strategy.</p>

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PET imaging of atherosclerotic plaques using the stabilin-2-targeted tracer 18F-S2P in preclinical models

  • 期刊论文

  • 发表日期：

    2026年7月4日

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  • Dilibire Adili,
  • Dongsheng Zhang,
  • Guangfa Wang,
  • Haocheng Jin,
  • Ke Sun,
  • Shanshan Zhao,
  • Junru Wu,
  • Chen Su,
  • Hongcheng Shi,
  • Zan Li,
  • Xinhui Su

摘要

Purpose

Elevated Stabilin-2 (STAB2) expression in macrophages within atherosclerotic plaques offers a promising molecular target for imaging vascular inflammation. The S2P peptide specifically binds STAB2. This study aims to evaluate the feasibility of using the STAB2-targeted 18F-labeled tracer (18F-S2P) for positron emission tomography (PET) imaging to identify atherosclerotic plaques.

Methods

Stab2 expression was validated via single-cell RNA sequencing of Ldlr−/− mouse samples. Biodistribution and micro-PET/CT imaging were performed in high-fat diet-fed Ldlr−/− mice (3–12 weeks) and chow-fed controls, with comparisons to 18F-FDG and 18F-Pentixafor. Plaque burden and macrophage infiltration were evaluated using Oil Red O, H&E, and immunofluorescence staining. Immunohistochemical staining was used to detect STAB2 expression in human atherosclerotic specimens.

Results

ScRNA-seq analysis identified Stab2 as a macrophage-specific marker in atherosclerosis plaque. In vivo micro-PET/CT quantification revealed disease duration-dependent uptake (1.41 ± 0.31 ID%/g at 3 weeks vs. 2.17 ± 0.19 ID%/g at 12 weeks, P < 0.0001), which positively correlated with histological plaque burden. 18F-S2P PET imaging demonstrated 5.4-fold higher plaque uptake in Ldlr−/− mice compared to wild-type controls (P < 0.0001), significantly outperforming 18F-FDG (1.52-fold) and 18F-Pentixafor (1.89-fold) in atherosclerotic lesions. Furthermore, STAB2 was also detectable in human atherosclerotic plaques.

Conclusion

This study introduces a novel STAB2-targeted PET probe (18F-S2P) for non-invasive imaging of atherosclerotic plaques in preclinical models, enabling the detection of atherosclerotic inflammation. The endogenous expression of STAB2 in human atherosclerotic lesions further strengthens the translational potential of this imaging strategy.