title: Effects of skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones.
abstract: Necrosis avid agents (NAAs) can be used for diagnose of necrosis-related diseases, evaluation of therapeutic responses and targeted therapeutics of tumor. In order to probe into the effects of molecular skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones, four dianthrone compounds with the same substituents but different skeletal structures, namely Hypericin (Hyp), protohypericin (ProHyp), emodin dianthrone mesomer (ED-1) and emodin dianthrone raceme (ED-2) were synthesized and radioiodinated. Then radioiodinated dianthrones were evaluated in vitro for their necrosis avidity in A549 lung cancer cells untreated and treated with H2O2. Their biodistribution and pharmacokinetic properties were determined in rat models of induced necrosis. In vitro cell assay revealed that destruction of rigid skeleton structure dramatically reduced their necrosis targeting ability. Animal studies demonstrated that destruction of rigid skeleton structure dramatically reduced the necrotic tissue uptake and speed up the clearance from the most normal tissues for the studied compounds. Among these (131)I-dianthrones, (131)I-Hyp exhibited the highest uptake and persistent retention in necrotic tissues. Hepatic infarction could be clearly visualized by SPECT/CT using (131)I-Hyp as an imaging probe. The results suggest that the skeleton structure of Hyp is the lead structure for further structure optimization of this class of NAAs.
authors.affiliation: a Laboratory of Translational Medicine , Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing, Jiangsu Province , P.R. China .|b Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing, Jiangsu Province , P.R. China .
authors.forename: Dongjian
authors.initials: D
authors.lastname: Zhang
authors.affiliation: a Laboratory of Translational Medicine , Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing, Jiangsu Province , P.R. China .
authors.forename: Cuihua
authors.initials: C
authors.lastname: Jiang
authors.affiliation: a Laboratory of Translational Medicine , Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing, Jiangsu Province , P.R. China .
authors.forename: Shengwei
authors.initials: S
authors.lastname: Yang
authors.affiliation: a Laboratory of Translational Medicine , Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing, Jiangsu Province , P.R. China .
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.affiliation: a Laboratory of Translational Medicine , Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing, Jiangsu Province , P.R. China .
authors.forename: Dejian
authors.initials: D
authors.lastname: Huang
authors.affiliation: a Laboratory of Translational Medicine , Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing, Jiangsu Province , P.R. China .
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Wang
authors.affiliation: c Department of Radiology , the First Affiliated Hospital of China Medical University , Shenyang, Liaoning Province , P.R. China .
authors.forename: Haibo
authors.initials: H
authors.lastname: Shao
authors.affiliation: a Laboratory of Translational Medicine , Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing, Jiangsu Province , P.R. China .|e Theragnostic Laboratory , Campus Gasthuisberg , KU Leuven, Leuven , Belgium.
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Feng
authors.affiliation: d Radiation Medical Institute , Shandong Academy of Medical Sciences , Jinan, Shandong Province , P.R. China , and.
authors.forename: Ziping
authors.initials: Z
authors.lastname: Sun
authors.affiliation: a Laboratory of Translational Medicine , Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing, Jiangsu Province , P.R. China .|d Radiation Medical Institute , Shandong Academy of Medical Sciences , Jinan, Shandong Province , P.R. China , and.|e Theragnostic Laboratory , Campus Gasthuisberg , KU Leuven, Leuven , Belgium.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
authors.affiliation: a Laboratory of Translational Medicine , Jiangsu Province Academy of Traditional Chinese Medicine , Nanjing, Jiangsu Province , P.R. China .
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: b Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing, Jiangsu Province , P.R. China .
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000818:Animals; D000873:Anthracenes; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D015195:Drug Design; D004642:Emodin / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000737:chemistry; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D008297:Male; D009336:Necrosis / Q000000981:diagnostic imaging*; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000873:Anthracenes; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; C108325:protohypericin; D010569:Perylene; C049933:emodin anthrone; C004965:hypericin; D006861:Hydrogen Peroxide; D004642:Emodin
keywords: Autoradiography; SPECT/CT imaging; biodistribution; necrosis targeting; pharmacokinetics; radioiodinated dianthrones