Preliminary evaluation of acute toxicity of (188) Re-BMEDA-liposome in rats.
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 ¹⁸⁸Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomes (¹⁸⁸Re-BMEDA-liposome) in Sprague-Dawley rats. Rats were administered with ¹⁸⁸Re-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 ¹⁸⁸Re-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 x 10³  µl⁻¹; male: 14.52 ± 5.12 to 1.43 ± 0.54 x 10³  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 ¹⁸⁸Re-BMEDA-liposome-treated and control groups. The frequencies of dicentric chromosomes were associated with dosage of ¹⁸⁸Re-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.
Liu
Chi-Mou
CM
Institute of Nuclear Energy Research, Tauyuan, Taiwan.
Chang
Chih-Hsien
CH
Chang
Ya-Jen
YJ
Hsu
Chin-Wei
CW
Chen
Liang-Cheng
LC
Chen
Hsiao-Lin
HL
Ho
Chung-Li
CL
Yu
Chia-Yu
CY
Chang
Tsui-Jung
TJ
Chiang
Tung-Chuan
TC
Lee
Te-Wei
TW
D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005029:Ethylenediamines; D005260:Female; D007275:Injections, Intravenous; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D009942:Organometallic Compounds; D011092:Polyethylene Glycols / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012211:Rhenium / Q000008:administration & dosage / Q000627:therapeutic use*; D023382:Toxicity Tests, Acute / Q000379:methods
C521828:188Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine; D002614:Chelating Agents; D005029:Ethylenediamines; D008081:Liposomes; D009942:Organometallic Compounds; D011092:Polyethylene Glycols; D012211:Rhenium