Scholarlink

<p>Extracellular arterial activity of the pro-inflammatory enzyme myeloperoxidase (MPO) destabilizes atherosclerotic plaque and associates with future atherothrombosis. To facilitate first-in-human studies using extracellular MPO activity as a molecular imaging target to identify high-risk atherosclerotic plaque, we describe [<sup>68</sup>Ga]Ga-IEMA, a NODAGA-based positron emission tomography (PET) radiotracer that provides an index for extracellular MPO activity. Synthesis of [<sup>68</sup>Ga]Ga-IEMA was achieved in five steps and with high radiolabelling efficiency. [<sup>68</sup>Ga]Ga-IEMA self-oligomerized and bound to proteins upon exposure to enzymatically active MPO, did not cross-cell membranes and was stable in human serum in vitro, while [<sup>68</sup>Ga]Ga-IEMA had favorable blood kinetics and stability in circulation in vivo. [<sup>68</sup>Ga]Ga-IEMA PET imaging in a mouse model of plaque instability revealed enhanced signal in unstable compared with stable plaque and plaque-free arteries. These data indicate that [<sup>68</sup>Ga]Ga-IEMA is a promising translational candidate for the non-invasive identification of high-risk atherosclerotic plaques and the evaluation of therapies targeting arterial inflammation.</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

Development and validation of an activatable PET radiotracer reporting extracellular myeloperoxidase activity for the detection of unstable atherosclerotic plaque

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月7日

查看全文
  • George P. Keeling,
  • Xiaoying Wang,
  • Weiyu Chen,
  • Nadia Chaher,
  • Ling Gao,
  • Marcelo E. Andia,
  • Sergey Tumanov,
  • Piotr Golda,
  • Mohammed M. Chowdhury,
  • Prakash Saha,
  • Lefteris Livieratos,
  • James Nadel,
  • Roland Stocker,
  • Alkystis Phinikaridou

摘要

Extracellular arterial activity of the pro-inflammatory enzyme myeloperoxidase (MPO) destabilizes atherosclerotic plaque and associates with future atherothrombosis. To facilitate first-in-human studies using extracellular MPO activity as a molecular imaging target to identify high-risk atherosclerotic plaque, we describe [68Ga]Ga-IEMA, a NODAGA-based positron emission tomography (PET) radiotracer that provides an index for extracellular MPO activity. Synthesis of [68Ga]Ga-IEMA was achieved in five steps and with high radiolabelling efficiency. [68Ga]Ga-IEMA self-oligomerized and bound to proteins upon exposure to enzymatically active MPO, did not cross-cell membranes and was stable in human serum in vitro, while [68Ga]Ga-IEMA had favorable blood kinetics and stability in circulation in vivo. [68Ga]Ga-IEMA PET imaging in a mouse model of plaque instability revealed enhanced signal in unstable compared with stable plaque and plaque-free arteries. These data indicate that [68Ga]Ga-IEMA is a promising translational candidate for the non-invasive identification of high-risk atherosclerotic plaques and the evaluation of therapies targeting arterial inflammation.