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

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 （1231-Hyp or 1311-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-radioac- tive 1271-Hyp in normal mice for 24 h and 14 d. Methods： Studies were performed on 132 normal mice. 12Zl -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, 1271-Hyp was administered intravenously at assumed values to bracket the value of LD5o. The rest 20 mice were used in the control groups. Results： At 24 h and 14 d following the injection of 1271 -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 LDso of 1271-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 1271-Hyp, which not only supports the use of z231-Hyp or 1311-Hyp in the necrosis targeting theragnostic strategy, but also serves as a valuable reference for exploring other possible applications for iodinated Hyp.