Effects of skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones
Dongjian Zhang
Cuihua Jiang
Shengwei Yang
Meng Gao
Dejian Huang
Xiaoning Wang
Haibo Shao
Yuanbo Feng
Ziping Sun
Yicheng Ni
Jian Zhang
Zhiqi Yin
10.6084/m9.figshare.1608349
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>
2015-11-20 00:00:00
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