Abstract
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.