A single-dose toxicity study on non-radioactive iodinated hypericin for a targeted anticancer therapy in mice

摘要

Aim: Hypericin (Hyp) and its radio-derivatives have been investigated in animal models with ischemic heart diseases and malignancies for diagnostic and therapeutic purposes.Before radioiodinated Hyp (123I-Hyp or 131I-Hyp) can be considered as a clinically useful drug,vigorous evaluations on its chemotoxicity are necessary.In the present study,we examined the toxicity of a single dose of non-radioactive 127I-Hyp in normal mice for 24 h and 14 d.Methods: Studies were performed on 132 normal mice.127I-Hyp at a clinically relevant dose of 0.1 mg/kg body weight and a 100-times higher dose of 10 mg/kg was intravenously injected into 40 mice.The safety aspects of clinical manifestations,serological biochemistry,and histopathology were assessed.In another 72 mice,127I-Hyp was administered intravenously at assumed values to bracket the value of LD50.The rest 20 mice were used in the control groups.Results: At 24 h and 14 d following the injection of 127I-Hyp at either 0.1 or 10 mg/kg,all mice tolerated well without mortality or any observable treatment-related symptoms.No significant differences were found in blood biochemical parameters between the test and control groups.All organs presented normal appearances upon histopathological inspection.The value of LD50 of 127I-Hyp in mice through intravenous injection was 20.26 mg/kg,with the 95％ confidence interval between 18.90 and 21.55 mg/kg.Conclusion: The current study reveals a broad safety range of 127I-Hyp,which not only supports the use of 123I-Hyp or 131I-Hyp in the necrosis targeting theragnostic strategy,but also serves as a valuable reference for exploring other possible applications for iodinated Hyp.