1-(meta-[211At]Astatobenzyl)guanidine: synthesis via astato demetalation and preliminary in vitro and in vivo evaluation

Abstract

No-carrier-added 1-(m-[211At]astatobenzyl)guanidine ([211At]MABG) was synthesized by astato demetalation using two different routes. The overall yield for the two-step approach from 3-(tri-n-butylstannyl)benzylamine was 13%. N-Chlorosuccinimide-mediated astato desilylation of 1-[3-(trimethylsilyl)benzyl]guanidine in acetic acid gave poor yields. In trifluoroacetic acid, the reaction worked well. The radiochemical yield was independent of reaction time and the amount of precursor used; however, the temperature of the reaction had a marked effect. Yields of 85% were obtained in 5 min at 70 degrees C using 0.5 mumol of the precursor. The percentage specific binding in vitro of [211At]MABG was nearly constant over a 2-log activity range and was comparable to that of no-carrier-added [131]MIBG. The accumulation of [211At]MABG in the heart and adrenals of normal mice was similar to that observed for no-carrier-added [131]MIBG.