Abstract
1207
Objectives Liposomes can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness as well as reducing toxicity. To evaluate therapeutic strategies, it is essential to use animal models reflecting important safety aspects before clinical application. Since our previous study found that high dosage (185 MBq) of 188Re-N,N-bis (2-mercaptoethyl)-N’,N’-diethylethylenediamine-labeled pegylated liposomes (188Re-liposome) induced decrease in white blood cell (WBC) count in Sprague-Dawley rats 7 days post-injection, the objective of this study was to investigate 28-day extended acute radiotoxicity of 188Re-liposome.
Methods Rats were administered via intravenous injection with 188Re-liposome (185 MBq, 55.5 MBq and 18.5 MBq), normal saline as blank control or non-radioactive liposome as vehicle control. Mortality, clinical signs, food consumption, body weights, urinary, biochemical and hematological analyses were examined. In addition, gross necropsy and histopathological examinations were also performed at the end of the follow-up period.
Results None of the rats died and no clinical sign was observed during the 28-day study period. Only male rats receiving 188Re-liposome at high dosage (185 MBq) displayed a slight weight loss compared with the control rats. In both male and female rats, the WBC counts of both high-dose and medium-dose (55.5 MBq) groups reduced significantly 7 days post injection, but recovered to normal range on Study Day 29. There was no significant difference in urinary analyses, biochemical parameters and histopathological assessments between the 188Re-liposome-treated and control groups.
Conclusions The information generated from this study on extended acute toxicity of 188Re-liposome will serve as a safety reference for radiopharmaceuticals in early-phase clinical trials