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Radioiodinated hypericin disulfonic acid sodium salts as a DNA-binding probe for early imaging of necrotic myocardium.

Necrotic myocardium imaging can provide great indicators of salvaged myocardial areas for clinical guidances to patients with myocardial infarction (MI). One of the key challenges in necrotic myocardium imaging however, is lack of ideal necrotic imaging tracers for exactly and timely depicting the necrotic myocardium. 131 I-hypericin (131 I-Hyp) is a promising tracer in exact necrotic myocardium delineation. However, it can't clearly image necrotic myocardium until 9h post injection (p.i.) for the high background signals in blood and lung due to the strong lipophilicity. Herein, an optimized 131 I-hypericin-2,5-disulfonic acid sodium salts (131 I-Shyp) probe was synthesized for better pharmacokinetic and biodistribution properties to necrosis imaging. And the related mechanisms of necrotic avidity ability of 131 I-Hyp and 131 I-Shyp were also explored. In the results, 131 I-Shyp still showed selectively high accumulation in both necrotic cells and tissues. Biodistribution data revealed the decreased uptake of 131 I-Shyp in normal organs (lung, spleen and heart) and blood (as shown in pharmacokinetics studies). 131 I-Shyp presented quicker and clearer imaging for necrotic myocardium at 4h p.i. compared with 131 I-Hyp, suggesting that improved hydrophilicity of 131 I-Shyp may be conducive to its better pharmacokinetic and biodistribution properties to imaging. Additionally, DNA competitive binding assays and blocking experiments indicated that E-DNA is the possible target of Shyp and Hyp for their necrosis avidity. 131 I-Shyp may serve as a potential E-DNA targeted probe for necrotic myocardium imaging with molecular specificity for clinical use.

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