Neurobehavioral assessment of BMEDA by modified Irwin test in Sprague-Dawley rats

Regul Toxicol Pharmacol. 2024 Nov:153:105703. doi: 10.1016/j.yrtph.2024.105703. Epub 2024 Sep 17.

Abstract

The neurobehavioral assessment of N,N-bis(2-mercapatoethly)-N',N'-diethylenediamine (BMEDA), which can form a chelate with rhenium-188 (188Re) to produce the 188Re-BMEDA-liposome, was evaluated. The purpose of this study was to evaluate the potential neurobehavioral changes by using the functional observational battery observation procedures when intravenous injection of BMEDA to Sprague-Dawley rats. Rats were administered BMEDA at dose levels of 1, 2, and 5 mg/kg. No mortalities were observed. There are some observations related to BMEDA treatment found in the 5 mg/kg dose group at 10 min post-dose. Tremor was observed in one male rat and seven female rats. The increased respiration, vocalization, not easy to handle and/or loss of tone in the limb were observed in both males and females, and increased body temperature was observed in male animals. Based on the results, a single intravenous dose of BMEDA administered to rats resulted in increased respiration, vocalization, not easy to handle and/or loss of tone in the limb increasing at the dose level of 5 mg/kg. No neurobehavioral effects were noted after BMEDA administration up to the dose level of 2 mg/kg. The information of this study will provides a point of reference to design appropriately therapeutic studies for future human use.

Keywords: (188)Re-BMEDA-Liposome; BMEDA; Neurotoxicology; Radiopharmaceutical; Sprague–Dawley rats.

MeSH terms

  • Animals
  • Behavior, Animal* / drug effects
  • Dose-Response Relationship, Drug
  • Ethylenediamines / pharmacology
  • Ethylenediamines / toxicity
  • Female
  • Male
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / toxicity
  • Rats
  • Rats, Sprague-Dawley*
  • Rhenium

Substances

  • Rhenium
  • Ethylenediamines
  • Organometallic Compounds