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Development of Duramycin-Based Molecular Probes for Cell Death Imaging

Authors
  • Zhang, Dongjian;
  • Gao, Meng;
  • Jin, Qiaomei;
  • Ni, Yicheng; 14498;
  • Li, Huailiang;
  • Jiang, Cuihua;
  • Zhang, Jian;
Publication Date
Feb 10, 2022
Source
Lirias
Keywords
License
Unknown
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Abstract

Cell death is involved in numerous pathological conditions such as cardiovascular disorders, ischemic stroke and organ transplant rejection, and plays a critical role in the treatment of cancer. Cell death imaging can serve as a noninvasive means to detect the severity of tissue damage, monitor the progression of diseases, and evaluate the effectiveness of treatments, which help to provide prognostic information and guide the formulation of individualized treatment plans. The high abundance of phosphatidylethanolamine (PE), which is predominantly confined to the inner leaflet of the lipid bilayer membrane in healthy mammalian cells, becomes exposed on the cell surface in the early stages of apoptosis or accessible to the extracellular milieu when the cell suffers from necrosis, thus representing an attractive target for cell death imaging. Duramycin is a tetracyclic polypeptide that contains 19 amino acids and can bind to PE with excellent affinity and specificity. Additionally, this peptide has several favorable structural traits including relatively low molecular weight, stability to enzymatic hydrolysis, and ease of conjugation and labeling. All these highlight the potential of duramycin as a candidate ligand for developing PE-specific molecular probes. By far, a couple of duramycin-based molecular probes such as Tc-99 m-, F-18-, or Ga-68-labeled duramycin have been developed to target exposed PE for in vivo noninvasive imaging of cell death in different animal models. In this review article, we describe the state of the art with respect to in vivo imaging of cell death using duramycin-based molecular probes, as validated by immunohistopathology. / status: published

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