10.6084/m9.figshare.1608349 Dongjian Zhang Dongjian Zhang Cuihua Jiang Cuihua Jiang Shengwei Yang Shengwei Yang Meng Gao Meng Gao Dejian Huang Dejian Huang Xiaoning Wang Xiaoning Wang Haibo Shao Haibo Shao Yuanbo Feng Yuanbo Feng Ziping Sun Ziping Sun Yicheng Ni Yicheng Ni Jian Zhang Jian Zhang Zhiqi Yin Zhiqi Yin Effects of skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones Taylor & Francis Group 2015 NAA 549 lung cancer cells radioiodinated dianthrones ED skeleton structure emodin dianthrone raceme H 2 O 2 tissue radioiodinated dianthrones Necrosis 131 I-Hyp clearance properties necrosis SPECT 2015-11-20 00:00:00 Journal contribution https://tandf.figshare.com/articles/journal_contribution/Effects_of_skeleton_structure_on_necrosis_targeting_and_clearance_properties_of_radioiodinated_dianthrones/1608349 <p>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 <i>in vitro</i> for their necrosis avidity in A549 lung cancer cells untreated and treated with H<sub>2</sub>O<sub>2</sub>. Their biodistribution and pharmacokinetic properties were determined in rat models of induced necrosis. <i>In vitro</i> 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 <sup>131</sup>I-dianthrones, <sup>131</sup>I-Hyp exhibited the highest uptake and persistent retention in necrotic tissues. Hepatic infarction could be clearly visualized by SPECT/CT using <sup>131</sup>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.</p>