Scholarlink

Purpose <p>PD-L1 PET imaging can provide a non-invasively and real-time assessment of PD-L1 expression status at tumor sites. This study aimed to evaluate the targeting efficacy and biodistribution of a novel peptide-based PD-L1 PET agent, [<sup>68</sup>Ga]Ga-DOTA-PEG<sub>2</sub>-Asp<sub>2</sub>-PDL1P, in preclinical studies and human participants.</p> Methods <p>[<sup>68</sup>Ga]Ga-DOTA-PEG<sub>2</sub>-Asp<sub>2</sub>-PDL1P was synthesized and the probe stability was analyzed in vitro and in vivo. Cellular uptake of the probe was evaluated using tumor cell lines with different PD-L1 expression levels. Small animal PET imaging and semi-quantitative studies were conducted in PC3, H1975 and A549 tumor-bearing mice models, with tumor PD-L1 expression confirmed through immunofluorescence and immunohistochemistry. Furthermore, [<sup>68</sup>Ga]Ga-DOTA-PEG<sub>2</sub>-Asp<sub>2</sub>-PDL1P PET imaging was performed in 1 healthy volunteer and 14 lung cancer patients to assess biodistribution and PD-L1 expression at tumor sites.</p> Results <p>[<sup>68</sup>Ga]Ga-DOTA-PEG<sub>2</sub>-Asp<sub>2</sub>-PDL1P exhibited a radiochemical purity of &gt; 99% and had good stability both in vitro and in vivo. In vitro cellular uptake and in vivo small animal PET imaging revealed the probe binding to PD-L1 with high affinity and specificity, consistent with the results of immunofluorescence and immunohistochemistry. In the clinical study involving 15 participants, [<sup>68</sup>Ga]Ga-DOTA-PEG<sub>2</sub>-Asp<sub>2</sub>-PDL1P was proven safe with demonstrating low uptake in normal organs and physiologically excreting via the urinary system. Lung cancer patients with high PD-L1 expression (TPS 70-90%) exhibited higher tumor uptake and tumor-to-background ratios than those with negative or low PD-L1 expression (TPS &lt; 1-10%), with SUVmax of 1.89–2.27 vs. 0.87–1.01, tumor-to-lung ratios of 4.73–7.68 vs. 1.61–2.35, and tumor-to-muscle ratios of 6.73–12.61 vs. 4.35–5.61.</p> Conclusion <p>[<sup>68</sup>Ga]Ga-DOTA-PEG<sub>2</sub>-Asp<sub>2</sub>-PDL1P showed promising as a PET agent to assess tumor PD-L1 expression in preclinical and first-in-human studies, offering a non-invasive, real-time and accurate tool to address clinical challenges in predicting and assessing the efficacy of immunotherapy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Preclinical and first‑in‑human evaluation of [68Ga]Ga-DOTA-PEG2-Asp2-PDL1P PET imaging to assess tumor PD-L1 expression

  • 期刊论文

  • 发表日期：

    2025年3月3日

查看全文
  • Yang Chen,
  • Yinting Hu,
  • Ao Li,
  • Guojin Zhang,
  • Danyi Guo,
  • Xinchao Yao,
  • Baozhen Zeng,
  • Ganghua Tang,
  • Benyuan Jiang,
  • Lei Jiang

摘要

Purpose

PD-L1 PET imaging can provide a non-invasively and real-time assessment of PD-L1 expression status at tumor sites. This study aimed to evaluate the targeting efficacy and biodistribution of a novel peptide-based PD-L1 PET agent, [68Ga]Ga-DOTA-PEG2-Asp2-PDL1P, in preclinical studies and human participants.

Methods

[68Ga]Ga-DOTA-PEG2-Asp2-PDL1P was synthesized and the probe stability was analyzed in vitro and in vivo. Cellular uptake of the probe was evaluated using tumor cell lines with different PD-L1 expression levels. Small animal PET imaging and semi-quantitative studies were conducted in PC3, H1975 and A549 tumor-bearing mice models, with tumor PD-L1 expression confirmed through immunofluorescence and immunohistochemistry. Furthermore, [68Ga]Ga-DOTA-PEG2-Asp2-PDL1P PET imaging was performed in 1 healthy volunteer and 14 lung cancer patients to assess biodistribution and PD-L1 expression at tumor sites.

Results

[68Ga]Ga-DOTA-PEG2-Asp2-PDL1P exhibited a radiochemical purity of > 99% and had good stability both in vitro and in vivo. In vitro cellular uptake and in vivo small animal PET imaging revealed the probe binding to PD-L1 with high affinity and specificity, consistent with the results of immunofluorescence and immunohistochemistry. In the clinical study involving 15 participants, [68Ga]Ga-DOTA-PEG2-Asp2-PDL1P was proven safe with demonstrating low uptake in normal organs and physiologically excreting via the urinary system. Lung cancer patients with high PD-L1 expression (TPS 70-90%) exhibited higher tumor uptake and tumor-to-background ratios than those with negative or low PD-L1 expression (TPS < 1-10%), with SUVmax of 1.89–2.27 vs. 0.87–1.01, tumor-to-lung ratios of 4.73–7.68 vs. 1.61–2.35, and tumor-to-muscle ratios of 6.73–12.61 vs. 4.35–5.61.

Conclusion

[68Ga]Ga-DOTA-PEG2-Asp2-PDL1P showed promising as a PET agent to assess tumor PD-L1 expression in preclinical and first-in-human studies, offering a non-invasive, real-time and accurate tool to address clinical challenges in predicting and assessing the efficacy of immunotherapy.