Meta‐[211AT]astatobenzylguanidine: Further evaluation of a potential therapeutic agent

Abstract

Meta-[²¹¹At]astatobenzylguanidine ([²¹¹At]MABG) is an astatinated analogue of meta-iodobenzylguanidine (MIBG) that could be of value for therapeutic applications. The initial goal of this study was to determine whether [²¹¹At]MABG is taken up, like MIBG, by a specific uptake-1 mechanism. Norepinephrine and desipramine (DMI) decreased [²¹¹At]MABG uptake in SK-N-SH human neuroblastoma cells. This uptake was found to be energy-dependent: In mice, pre-treatment with DMI reduced uptake of[²¹¹At]MABG at 1 hr post-injection in the adrenal and in the heart. Tetrabenazine at a dose of 40 mg/kg reduced uptake of [²¹¹At]MABG in the mouse heart in vivo (69% of control) whereas up to 100 μM of tetrabenazine did not affect the in vitro uptake of [²¹¹At]MABG in SK-N-SH cells. In SK-N-SH cells, 53% and 38%, respectively, of the initial uptake of [²¹¹At]MABG was retained at 4 hr and 6 hr. For no-carrieradded (n. c.a.) [¹²¹I]MIBG these values were similar, 60% and 48%. The ability of SK-N-SH cells to incorporate [³H]thymidine was reduced to less than 50% of control values when treated with as little as 3.2 nCi of [²¹¹At]MABG. In contrast, no significant reduction in the thymidine uptake was observed, even with 80 nCi of n. c.a. MIBG.