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-I 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 microM 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-carrier-added (n.c.a.) [131I]
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.