<p>Fluorescent molecules with specific target moieties are essential for histopathological analysis, but their limited tissue penetration depth makes in vivo, in situ color encoding analysis challenging. Magnetic resonance imaging (MRI) offers deep tissue penetration. When combined with chemical shift-encoded MRI reporters, it enables in vivo chemical shift encoding for biotarget imaging and analysis. These reporters require both strong signal intensity and large chemical shift window. However, conventional proton MRI reporters, with low sensitivity and a small chemical shift window, limit their in vivo applications. Here, we describe a chemical shift-encoded hyperpolarized <sup>129</sup>Xe MRI reporter based on the multivariate metal-organic framework, NiZn-ZIF-8, to overcome these challenges. The proposed NiZn-ZIF-8 gives distinct chemical shifts for dissolved and entrapped <sup>129</sup>Xe without signal interference, enhancing the <sup>129</sup>Xe NMR signal by 210 times compared to dissolved <sup>129</sup>Xe in water and biological media. This enables detection threshold at ≈&#xa0;4 fM concentrations, setting a record for the lowest concentration of xenon hosts detected in nanomaterials. Additionally, NiZn-ZIF-8 exhibits good in vivo MRI performance, allowing xenon encoding and distinction in rat lungs. NiZn-ZIF-8 represents a versatile and powerful platform for advanced molecular imaging and in vivo biomedical diagnostics.</p>

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Multivariate metal-organic frameworks enable chemical shift-encoded MRI with femtomolar sensitivity for biological systems

  • Qingbin Zeng,
  • Quer Yue,
  • Ming Zhang,
  • Rui Zhou,
  • Zhen Wang,
  • Zhongyu Xiao,
  • Yaping Yuan,
  • Xiuchao Zhao,
  • Weiping Jiang,
  • Lei Zhang,
  • Yuqi Yang,
  • Minghui Yang,
  • Haidong Li,
  • Louis-S. Bouchard,
  • Qianni Guo,
  • Xin Zhou

摘要

Fluorescent molecules with specific target moieties are essential for histopathological analysis, but their limited tissue penetration depth makes in vivo, in situ color encoding analysis challenging. Magnetic resonance imaging (MRI) offers deep tissue penetration. When combined with chemical shift-encoded MRI reporters, it enables in vivo chemical shift encoding for biotarget imaging and analysis. These reporters require both strong signal intensity and large chemical shift window. However, conventional proton MRI reporters, with low sensitivity and a small chemical shift window, limit their in vivo applications. Here, we describe a chemical shift-encoded hyperpolarized 129Xe MRI reporter based on the multivariate metal-organic framework, NiZn-ZIF-8, to overcome these challenges. The proposed NiZn-ZIF-8 gives distinct chemical shifts for dissolved and entrapped 129Xe without signal interference, enhancing the 129Xe NMR signal by 210 times compared to dissolved 129Xe in water and biological media. This enables detection threshold at ≈ 4 fM concentrations, setting a record for the lowest concentration of xenon hosts detected in nanomaterials. Additionally, NiZn-ZIF-8 exhibits good in vivo MRI performance, allowing xenon encoding and distinction in rat lungs. NiZn-ZIF-8 represents a versatile and powerful platform for advanced molecular imaging and in vivo biomedical diagnostics.