Radiolabeling of lacosamide using highly purified rhenium-188 as a prospective brain theranostic agent

Abstract

Rhenium-188 is prospectively effective for both diagnosis and radiotherapy as it appropriately emits gamma rays and beta particles. Lacosamide (LCM) is a newly approved antiepileptic medication for focal drug-resistant epilepsy. Rhenium-188 was separated with high elution yield and high purity using the new 188W/188Re generator based on the ZrSiW gel matrix. 188Re-LCM was prepared with high radiochemical yield and high purity. Biodistribution of 188Re-LCM in normal Swiss albino mice was investigated to determine its utility as a potential brain therapy agent. The 188W/188Re generator was used to obtain 188Re based on the ZrSi188W gel matrix, and the chemical, radiochemical, and radionuclidic purity of the obtained 188Re was determined using inductively coupled plasma optical emission spectrometry (ICP-AES), a paper chromatography technique, and high-purity germanium (HPGe) detection, respectively, to assess its validity for LCM labeling. Various factors, such as the pH, reaction time, and LCM quantity, were therefore studied in order to improve the yield and purity of 188Re-LCM, as determined by various chromatographic techniques such as electrophoresis, thin layer chromatography (TLC), and high-pressure liquid chromatography (HPLC). 188Re was obtained with a high elution yield (75 ± 3%) and a low 188W breakthrough (0.001 ± 0.0001%). The maximum radiochemical yield of 188Re-LCM (87.5 ± 1.8%) was obtained using 50 μl LCM (4 mM), 250 μl stannous chloride (4.4 mM) at pH 4, 100 μl 188Re (37 MBq), within 30 min, at room temperature (25 ± 3 °C), as determined by TLC, electrophoresis, and HPLC techniques. Biodistribution analysis showed that 188Re-LCM was primarily localized in the brain (5.1%) with a long residence time (240 min).