PMID- 28414189 OWN - NLM STAT- MEDLINE DCOM- 20180405 LR - 20211204 IS - 1873-3441 (Electronic) IS - 0939-6411 (Linking) VI - 117 DP - 2017 Aug TI - Radioiodinated hypericin disulfonic acid sodium salts as a DNA-binding probe for early imaging of necrotic myocardium. PG - 151-159 LID - S0939-6411(16)30416-7 [pii] LID - 10.1016/j.ejpb.2017.04.006 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Duan, Xinghua AU - Duan X AD - Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Affiliated Hospital of Integrated Traditional Chinese & Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China. FAU - Yin, Zhiqi AU - Yin Z AD - Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China. FAU - Jiang, Cuihua AU - Jiang C AD - Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Affiliated Hospital of Integrated Traditional Chinese & Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China. FAU - Jin, Qiaomei AU - Jin Q AD - Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Affiliated Hospital of Integrated Traditional Chinese & Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China. FAU - Zhang, Dongjian AU - Zhang D AD - Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Affiliated Hospital of Integrated Traditional Chinese & Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China. FAU - Sun, Ziping AU - Sun Z AD - Radiation Medical Institute, Shandong Academy of Medical Sciences, Jinan 250062, Shandong Province, PR China. FAU - Ye, Wencai AU - Ye W AD - Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou 510632, Guangdong Province, PR China. Electronic address: chyewc@gmail.com. FAU - Zhang, Jian AU - Zhang J AD - Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Affiliated Hospital of Integrated Traditional Chinese & Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China. Electronic address: zjwonderful@hotmail.com. LA - eng PT - Journal Article DEP - 20170413 PL - Netherlands TA - Eur J Pharm Biopharm JT - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JID - 9109778 RN - 0 (Anthracenes) RN - 0 (Iodine Radioisotopes) RN - 0 (Sulfonic Acids) RN - 5QD5427UN7 (Perylene) RN - 7V2F1075HD (hypericin) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Anthracenes MH - Cattle MH - Cell Line MH - Cell Survival/physiology MH - DNA/*metabolism MH - Heart/*diagnostic imaging MH - Iodine Radioisotopes/*metabolism MH - Male MH - Mice MH - Myocardium/*metabolism MH - Necrosis/diagnostic imaging/metabolism MH - Perylene/*analogs & derivatives/metabolism MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Sulfonic Acids/*metabolism OTO - NOTNLM OT - Drug targeted OT - Extracellular DNA OT - Hydrophilicity OT - Necrotic myocardium imaging OT - Pharmacokinetic OT - Radioiodinated hypericin-2,5-disulfonic acid sodium salts EDAT- 2017/04/18 06:00 MHDA- 2018/04/06 06:00 CRDT- 2017/04/18 06:00 PHST- 2016/08/05 00:00 [received] PHST- 2017/04/01 00:00 [revised] PHST- 2017/04/06 00:00 [accepted] PHST- 2017/04/18 06:00 [pubmed] PHST- 2018/04/06 06:00 [medline] PHST- 2017/04/18 06:00 [entrez] AID - S0939-6411(16)30416-7 [pii] AID - 10.1016/j.ejpb.2017.04.006 [doi] PST - ppublish SO - Eur J Pharm Biopharm. 2017 Aug;117:151-159. doi: 10.1016/j.ejpb.2017.04.006. Epub 2017 Apr 13.