Evaluation of Radioiodinated 1,4-Naphthoquinones as Necrosis Avid Agents for Rapid Myocardium Necrosis Imaging.

Purpose: Identifying necrotic myocardium in ischemic regions is of great importance for risk stratification and clinical decision-making. However, rapid noninvasive imaging of necrotic myocardium is still challenging. This study sought to evaluate the potential of 1,4-naphthoquinones to rapidly visu...

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Published in:Molecular Imaging & Biology Vol. 20; no. 1; pp. 74 - 85
Main Authors: Su, Chang, Zhang, Dongjian, Bao, Na, Ji, Aiyan, Feng, Yuanbo, Chen, Li, Ni, Yicheng, Zhang, Jian, Yin, Zhiqi
Format: diagnostic images pictorial research tables/charts Journal Article
Published: Springer Nature Feb2018
Online Access:View this record in EBSCOhost
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      dt: Feb2018
      vid: 20
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s11307-017-1089-3
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        atl: Evaluation of Radioiodinated 1,4-Naphthoquinones as Necrosis Avid Agents for Rapid Myocardium Necrosis Imaging.
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        au:
          Su, Chang
          Zhang, Dongjian
          Bao, Na
          Ji, Aiyan
          Feng, Yuanbo
          Chen, Li
          Ni, Yicheng
          Zhang, Jian
          Yin, Zhiqi
        affil: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24, Tongjiaxiang, Gulou District, 210009, Nanjing, Jiangsu Province, People’s Republic of China
      sug:
        subj:
          Myocardium Pathology
          Iodine Radioisotopes
          Quinones
          Diagnostic Imaging
          Chromatography, Liquid
          Molecular Structure
          Quinones Pharmacokinetics
          Animal Studies
          Models, Biological
          Chromatography, High Pressure Liquid
          Necrosis
          DNA Metabolism
          Spectrophotometry
          Mice
          Tomography, Emission-Computed, Single-Photon
          Rats
          Radiography
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
      ab: Purpose: Identifying necrotic myocardium in ischemic regions is of great importance for risk stratification and clinical decision-making. However, rapid noninvasive imaging of necrotic myocardium is still challenging. This study sought to evaluate the potential of 1,4-naphthoquinones to rapidly visualize necrotic myocardium and the possible mechanisms of necrosis avidity.Procedures: Six 1,4-naphthoquinones were radiolabeled with iodine-131 and the necrosis avidity was estimated in mouse models with muscular necrosis by gamma counting and autoradiography. The necrotic myocardium imaging property and biodistribution of [131I]naphthazarin (6) were determined in rat models with re-perfused myocardial infarction. A possible mechanism of necrosis avidity was explored by in vitro DNA-binding and in vivo blocking experiments.Results: The radiochemical purities of the six radiotracers were greater than 95 %. The uptakes in necrotic muscles of all six radiotracers were higher than those in viable muscles, and [131I]naphthazarin (6) showed the highest necrotic-to-viable ratio and necrosis-to-blood ratio at all tested time points. The necrotic myocardium could be clearly visualized by single-photon emission computed tomography/x-ray computed tomography (SPECT/CT) using [131I]naphthazarin (6) as early as 3 h post-injection. Post-mortem biodistribution showed the uptake of [131I]naphthazarin (6) in necrotic myocardium was 11.67-fold higher than that in viable myocardium. Absorption spectra and emission spectra suggested naphthazarin (6) could bind to DNA through intercalation. The uptake of [131I]naphthazarin (6) in necrotic muscle could be significantly blocked by excessive ethidium bromide (a typical DNA intercalator) and cold naphthazarin (6) with 63.49 and 71.96 % decline at 3 h post-injection in vivo, respectively.Conclusions: 1,4-Naphthoquinones retained necrosis avidity and [131I]naphthazarin (6) rapidly visualized necrotic myocardium. The necrosis avidity mechanism of [131I]naphthazarin (6) may be attributed to its binding with exposed DNA in necrotic tissues.
      pubtype: Academic Journal
      doctype:
        diagnostic images
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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