PT - JOURNAL ARTICLE AU - Batra, Vandana AU - Makvandi, Mehran AU - Ranieri, Pietro AU - Tsang, Matthew AU - Hou, Catherine AU - Li, Yimei AU - Vaidyanathan, Ganesan AU - Maris, John AU - Pryma, Daniel TI - Preclinical development of Meta-[<sup>211</sup>At]astatobenzylguanidine ([<sup>211</sup>At]MABG) as an alpha particle emitting systemic targeted radiotherapeutic for neuroblastoma (NB). DP - 2015 May 01 TA - Journal of Nuclear Medicine PG - 1264--1264 VI - 56 IP - supplement 3 4099 - http://jnm.snmjournals.org/content/56/supplement_3/1264.short 4100 - http://jnm.snmjournals.org/content/56/supplement_3/1264.full SO - J Nucl Med2015 May 01; 56 AB - 1264 Objectives NB is a radiosensitive childhood malignancy that frequently shows robust expression of the norepinephrine transporter (NET) on the tumor cell surface. NET-ligand therapy with [131I]MIBG is inefficient in tumor microclusters because of the relatively long path-length of β-particles. Targeted radiotherapy with the α-particle emitting NET-ligand [211At]MABG has the potential to deliver lethal radiation doses to sites of minimal residual disease because of the higher linear energy transfer and short path length of α-particles.Methods 211At was produced at the UPenn cyclotron facility with dry distillation to isolate 211At. Solid-phase radiosynthesis of [211At]MABG utilized Ultratrace resin. [211At]MABG uptake assays as well as biodistribution experiments were performed using NET transfected NB cell lines. In vivo dose escalation studies with [211At]MABG to determine radiotoxicology are ongoing. Finally, clonogenic assays and therapeutic trials in mouse models with [211At]MABG are also ongoing.Results We synthesized [211At]MABG (radiochemical yield of 50-60%, radiochemical purity &gt; 95%) and showed NET-specific uptake. NET-overexpressing lines demonstrated tumor-specific [211At]MABG uptake in vivo with tumor-muscle ratios of 7.37. Toxicity studies have shown that doses of 10 and 25 uCi of [211At]MABG were well tolerated. Clonogenic assays show [211At]MABG to be potently cytotoxic and murine efficacy studies are ongoing.Conclusions We have synthesized 211At-MABG in quantities sufficient for our preclinical experiments and are scaling production for clinical trials. [211At]MABG biodistribution and toxicity parameters are similar to the currently used radiotherapeutic [131I]MIBG. Our preliminary in-vitro data suggests that [211At]MABG may be an effective agent for salvage therapy for children with refractory/relapsed NB.Research Support Department of Defense (DoD) PRMRP Grant PressOn Foundation Progenics Pharmaceuticals