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<p>Trophoblast cell surface antigen 2 (Trop2) has been widely characterized as a clinically significant pan-cancer biomarker expressed in various tumors, significantly impacting tumor growth, invasion, and metastasis. In this study, we develop Trop2 targeting peptide-based radiotracer [<sup>68</sup>Ga]Ga-NOTA-GL10 for accurately detecting the Trop2 expression levels through positron emission tomography (PET) imaging. The Trop2-targeting peptide GL10 was rationally designed through computational methods based on the T2-2 peptide, and conjugated with the 1,4,7-triazacyclononane-<i>N,N′,N″</i>-triacetic acid (NOTA) chelator to synthesize the precursor NOTA-GL10 with nanomolar affinity for Trop2 (<i>K</i><sub>D</sub> = 12.9 nM). The radiosynthesis of [<sup>68</sup>Ga]Ga-NOTA-GL10 was achieved via conventional methods with high radiochemical yield (RCY), good stability, and favorable pharmacokinetics. Dynamic PET imaging revealed that the tracer presented a significantly higher tumor uptake ((5.03 ± 0.49)%ID/mL) and tumor-to-muscle ratio (4.44 ± 0.30) in Trop2-positive BxPC-3 xenografts compared to that in Trop2-negative PANC-1 xenografts ((1.41 ± 0.13)%ID/mL, 1.23 ± 0.27). Moreover, near-infrared (NIR) fluorescence imaging of the probe ICG-GL10 further confirmed the ability of GL10 to specifically target Trop2-positive tumors. The peptide-based Trop2 targeting radiotracer [<sup>68</sup>Ga]Ga-NOTA-GL10 demonstrated high specificity and sensitivity in detecting Trop2 expression, which revealed the potential of Trop2-based non-invasive imaging for cancer diagnosis.</p>

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In silico design and preclinical evaluation of a novel Trop2-targeted peptide tracer for PET imaging of tumors

  • 期刊论文

  • 发表日期：

    2025年10月10日

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  • Jing Fang,
  • Yan Xue,
  • Yuan Zha,
  • Ling Wang,
  • Zhihong Huang,
  • Shuang Wang,
  • Xue Zhu,
  • Ke Wang

摘要

Trophoblast cell surface antigen 2 (Trop2) has been widely characterized as a clinically significant pan-cancer biomarker expressed in various tumors, significantly impacting tumor growth, invasion, and metastasis. In this study, we develop Trop2 targeting peptide-based radiotracer [68Ga]Ga-NOTA-GL10 for accurately detecting the Trop2 expression levels through positron emission tomography (PET) imaging. The Trop2-targeting peptide GL10 was rationally designed through computational methods based on the T2-2 peptide, and conjugated with the 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) chelator to synthesize the precursor NOTA-GL10 with nanomolar affinity for Trop2 (KD = 12.9 nM). The radiosynthesis of [68Ga]Ga-NOTA-GL10 was achieved via conventional methods with high radiochemical yield (RCY), good stability, and favorable pharmacokinetics. Dynamic PET imaging revealed that the tracer presented a significantly higher tumor uptake ((5.03 ± 0.49)%ID/mL) and tumor-to-muscle ratio (4.44 ± 0.30) in Trop2-positive BxPC-3 xenografts compared to that in Trop2-negative PANC-1 xenografts ((1.41 ± 0.13)%ID/mL, 1.23 ± 0.27). Moreover, near-infrared (NIR) fluorescence imaging of the probe ICG-GL10 further confirmed the ability of GL10 to specifically target Trop2-positive tumors. The peptide-based Trop2 targeting radiotracer [68Ga]Ga-NOTA-GL10 demonstrated high specificity and sensitivity in detecting Trop2 expression, which revealed the potential of Trop2-based non-invasive imaging for cancer diagnosis.