A kit method for the high level synthesis of [211At]MABG

meta-[211At]Astatobenzylguanidine ([211At]MABG), an analogue of meta-iodobenzylguanidine (MIBG) labeled with the α-emitter 211At, targets the norepinephrine transporter. Because MABG has been shown to have excellent characteristics in preclinical studies, it has been considered to be a promising targeted radiotherapeutic for the treatment of tumors such as micrometastatic neuroblastoma that overexpress the norepinephrine transporter. To facilitate clinical evaluation of this agent, a convenient method for the high level synthesis of [211At]MABG that is adaptable for kit formulation has been developed. A tin precursor anchored to a solid-support was treated with a methanolic solution of 211At in the presence of a mixture of H2O2/HOAc as the oxidant; [211At]MABG was isolated by simple solid-phase extraction. By using C-18 solid-phase extraction, the radiochemical yield from 25 batches was 63 ± 13%; however, loss of radioactivity during evaporation of the methanolic solution was a problem. This difficulty was avoided by use of a cation exchange resin cartridge for isolation of [211At]MABG, which resulted in radiochemical yields of 63 ± 9% in a shorter duration of synthesis. The radiochemical purity was more than 90% and no chemical impurity has been detected. The final doses were sterile and apyrogenic. These results demonstrate that [211At]MABG can be prepared via a kit method at radioactivity levels anticipated for initiation of clinical studies.

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