title: A single-dose toxicity study on non-radioactive iodinated hypericin for a targeted anticancer therapy in mice.
abstract: OBJECTIVE
  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 ((123)I-Hyp or (131)I-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 (127)I-Hyp in normal mice for 24 h and 14 d.
  
  
  METHODS
  Studies were performed on 132 normal mice. (127)I -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, (127)I-Hyp was administered intravenously at assumed values to bracket the value of LD(50). The rest 20 mice were used in the control groups.
  
  
  RESULTS
  At 24 h and 14 d following the injection of (127)I -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 LD(50) of (127)I-Hyp in mice through intravenous injection was 20.26 mg/kg, with the 95% confidence interval between 18.90 and 21.55 mg/kg.
  
  
  CONCLUSIONS
  The current study reveals a broad safety range of (127)I-Hyp, which not only supports the use of (123)I-Hyp or (131)I-Hyp in the necrosis targeting theragnostic strategy, but also serves as a valuable reference for exploring other possible applications for iodinated Hyp.
authors.affiliation: Theragnostic Laboratory, Department of Imaging and Pathology, Biomedical Sciences Group, KU Leuven, Belgium.
authors.forename: Jun-jie
authors.initials: JJ
authors.lastname: Li
authors.forename: Marlein Miranda
authors.initials: MM
authors.lastname: Cona
authors.forename: Yuan-bo
authors.initials: YB
authors.lastname: Feng
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Guo-zhi
authors.initials: GZ
authors.lastname: Zhang
authors.forename: Xue-bin
authors.initials: XB
authors.lastname: Fu
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.forename: Raymond
authors.initials: R
authors.lastname: Oyen
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
authors.forename: Yi-cheng
authors.initials: YC
authors.lastname: Ni
mesh_terms: D000818:Animals; D000873:Anthracenes; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D005260:Female; D007456:Iodine Isotopes; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009928:Organ Specificity; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000873:Anthracenes; D000972:Antineoplastic Agents, Phytogenic; D007456:Iodine Isotopes; D010569:Perylene; C004965:hypericin