Institute of Nuclear Energy Research, Taoyuan, Taiwan.
J Appl Toxicol. 2013 Sep;33(9):886-93. doi: 10.1002/jat.2751. Epub 2012 Apr 26.
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. As our previous study found that a high dosage (185 of MBq) of (188) Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine-labeled pegylated liposomes ((188) Re-liposome) induced a decrease in white blood cell (WBC) count in Sprague-Dawley rats 7 days postinjection, the objective of the present study was to investigate extended acute radiotoxicity of (188) Re-liposome. Rats were administered via intravenous (i.v.) injection with (188) Re-liposome (185, 55.5 and 18.5 MBq), normal saline as a blank control or non-radioactive liposome as a vehicle control. Mortality, clinical signs, food consumption, body weights, urinary, biochemical and hematological analyzes were examined. In addition, gross necropsy and histopathological examinations were also performed at the end of the follow-up period. None of the rats died and no clinical sign was observed during the 28-day study period. Only male rats receiving (188) Re-liposome at a 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 postinjection, but recovered to the normal range on Study Day 29. There was no significant difference in urinary analyzes, biochemical parameters and histopathological assessments between the (188) Re-liposome-treated and control groups. The information generated from the present study on extended acute toxicity of (188) Re-liposome will serve as a safety reference for radiopharmaceuticals in early-phase clinical trials.
脂质体可以选择性地靶向癌症部位并携带有效载荷，从而提高诊断和治疗效果，降低毒性。在临床应用之前，评估治疗策略，使用反映重要安全方面的动物模型是至关重要的。正如我们之前的研究发现，高剂量（185MBq）的（188）Re-N，N-双（2-巯基乙基）-N'，N'-二乙基亚乙基二胺标记的聚乙二醇化脂质体（（188）Re-脂质体）在注射后 7 天导致 Sprague-Dawley 大鼠白细胞（WBC）计数下降，本研究的目的是研究（188）Re-脂质体的扩展急性放射毒性。大鼠通过静脉（i.v.）注射（188）Re-脂质体（185、55.5 和 18.5MBq）、生理盐水作为空白对照或非放射性脂质体作为载体对照进行给药。检测死亡率、临床症状、食物消耗、体重、尿液、生化和血液分析。此外，在随访结束时还进行了大体解剖和组织病理学检查。在 28 天的研究期间，没有大鼠死亡，也没有观察到临床症状。只有接受高剂量（185MBq）（188）Re-脂质体的雄性大鼠与对照组大鼠相比显示出轻微的体重减轻。在雄性和雌性大鼠中，高剂量和中剂量（55.5MBq）组的 WBC 计数在注射后 7 天显著降低，但在研究第 29 天恢复到正常范围。（188）Re-脂质体处理组与对照组之间的尿液分析、生化参数和组织病理学评估没有显著差异。本研究中关于（188）Re-脂质体的扩展急性毒性的信息将为放射性药物在早期临床试验中的安全性提供参考。
