title: 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-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.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC 27710.
authors.forename: G
authors.initials: G
authors.lastname: Vaidyanathan
authors.forename: D K
authors.initials: DK
authors.lastname: Strickland
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D019797:3-Iodobenzylguanidine; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001246:Astatine / Q000008:administration & dosage*; D001692:Biological Transport; D006146:Guanidines / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007462:Iodobenzenes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012110:Reserpine / Q000494:pharmacology; D013747:Tetrabenazine / Q000494:pharmacology; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006146:Guanidines; D007462:Iodobenzenes; C078685:1-(3-astatobenzyl)guanidine; D019797:3-Iodobenzylguanidine; D012110:Reserpine; D001246:Astatine; D013747:Tetrabenazine