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Preliminary evaluation of acute toxicity of 188 Re–BMEDA–liposome in rats
Author(s) -
Liu ChiMou,
Chang ChihHsien,
Chang YaJen,
Hsu ChinWei,
Chen LiangCheng,
Chen HsiaoLin,
Ho ChungLi,
Yu ChiaYu,
Chang TsuiJung,
Chiang TungChuan,
Lee TeWei
Publication year - 2010
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1541
Subject(s) - liposome , toxicity , medicine , acute toxicity , body weight , saline , chronic toxicity , pharmacology , nuclear medicine , physiology , pathology , chemistry , biochemistry
Liposomes can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. To evaluate therapeutic strategies, it is essential to use animal models reflecting important safety aspects before clinical application. The objective of this study was to investigate acute radiotoxicity of 188 Re‐ N , N ‐bis (2‐mercaptoethyl)‐ N ′,N′‐diethylethylenediamine (BMEDA)‐labeled pegylated liposomes ( 188 Re–BMEDA–liposome) in Sprague–Dawley rats. Rats were administered with 188 Re–BMEDA–liposome, normal saline as blank or non‐radioactive liposome as vehicle control via intravenous injection and observed for 14 days. Examinations were conducted with respect to mortality, clinical signs, food consumption, body weight and hematological and biochemical analyses. In addition, gross necropsy, histopathological examinations and cytogenetic analyses were also performed. None of the rats died and no clinical sign was observed during the 14‐day study period. Rats administered with 188 Re–BMEDA–liposome at dosage of 185 MBq displayed a significant weight loss compared with the control from study day (SD) 1 to SD 4, and the white blood cell count reduced to 5–10% of initial value (female: 18.55 ± 6.58 to 0.73 ± 0.26 × 10 3 µl −1 ; male: 14.52 ± 5.12 to 1.43 ± 0.54 × 10 3 µl −1 ) 7 days‐post injection, but were found to have recovered on SD 15. There were no significant differences in biochemical parameters and histopathological assessments between the 188 Re–BMEDA–liposome‐treated and control groups. The frequencies of dicentric chromosomes were associated with dosage of 188 Re–BMEDA–liposome. The information generated from this study on acute toxicity will serve as a safety reference for further subacute toxicity study in rats and human clinical trials. Copyright © 2010 John Wiley & Sons, Ltd.