Acute intravenous injection toxicity of BMEDA in mice

Abstract

(188)Re/(186)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine-labeled pegylated liposome ((188)Re-BMEDA-liposome) has been proven as a promising candidate for cancer therapy in tumor-rodent models. (188)Re-BMEDA complexes should be prepared for the radiolabeling of liposomes. This article describes the acute toxicity of BMEDA in Imprinting Control Region (ICR) mice. Treated mice were administered with BMEDA at dose levels of 3, 6, 9, and 12 mg/kg, with a dose volume of 10 mL/kg. The control mice were administered 10 mL/kg of vehicle control. The mice were observed for 14 days. Observations included mortality, clinical signs, total body-weight gains, food consumption, and gross necropsy findings. BMEDA exerted no adverse toxic effects in ICR mice at dose levels 3 mg/kg, which are up to 360,000 times higher than the intended human dose. The lethal-dose (LD(50)) value of BMEDA was 8.13 and 8.68 mg/kg in male and female mice, respectively.

Pharmacokinetics of BMEDA after Intravenous Administration in Beagle Dogs

“…However, prior to the Investigational New Drug application, where an estimate of drug’s safety for initial human use should be performed, both animal pharmacology and toxicology studies for both the 188 Re-BMEDA-liposome as well as the BMEDA must be performed, since BMEDA is a particular ingredient in the 188 Re-BMEDA-liposome. Within a 14-day period, the extended acute toxicity of BMEDA had been evaluated in ICR mice where the No Observed Adverse Effect Level (NOAEL) of BMEDA for them was 3 mg/kg [21]. Likewise, the NOAEL of BMEDA in Beagle dogs was 1 mg/kg [22].…”

Preliminary evaluation of acute toxicity of 188Re–BMEDA–liposome in rats

“…In our previous findings, 188 Re–BMEDA–liposome has been proved as a promising candidate for cancer therapy in C26 murine colon carcinoma ascites (Chang et al ., 2008; Chen et al ., 2007, 2008), solid tumor model (Chang et al ., 2007, 2008, 2010) and human colorectal solid tumor model (Chen et al ., 2010). In addition, an acute toxicity study of BMEDA in mice was also performed in our laboratory (Chang et al ., in press). Because the radiotoxicological data of 188 Re–BMEDA–liposome were limited, a toxicity test of 188 Re–BMEDA–liposome in Sprague–Dawley rats was performed in this study.…”