RT Journal Article
SR Electronic
T1 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).
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1264
OP 1264
VO 56
IS supplement 3
A1 Batra, Vandana
A1 Makvandi, Mehran
A1 Ranieri, Pietro
A1 Tsang, Matthew
A1 Hou, Catherine
A1 Li, Yimei
A1 Vaidyanathan, Ganesan
A1 Maris, John
A1 Pryma, Daniel
YR 2015
UL http://jnm.snmjournals.org/content/56/supplement_3/1264.abstract
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