Therapeutic efficacy of α-emitter meta-211At-astato-benzylguanidine (MABG) in a pheochromocytoma model

468 Objectives Beta-emitting meta-131I-iodo-benzylguanidine (MIBG) has been used in the treatment of malignant pheochromocytoma (PHEO). However the effects of MIBG and 5-year survival are limited. Thus, alternative effective treatment options are being sought. Alpha-emitters strongly suppress the growth of tumor cells. 211Astatine (211At) is an α-emitting halogen and has a suitable half-life for cancer therapy (t1/2=7.2 h). Therefore, meta-211At-astato-benzylguanidine (MABG) may potentially suppress the growth of malignant PHEO. However, to date there has been no data looking at the therapeutic effect of MABG in malignant PHEO. The purpose of the present study was to investigate the therapeutic effects of MABG in a rat PHEO model both in vitro and in vivo. Methods 211At was produced via the 209Bi(α,2n)211At reaction and was isolated through dry distillation. MABG was synthesized by astatination of meta-trimethylsilylbenzylguanidine hemisulfate in the presence of N-chlorosuccinimide as an oxidant. Cellular radiopharmaceutical uptake and tumor suppressive effects of MABG were examined using a rat PHEO cell line, PC-12. Biodistribution (n=4) and MABG therapeutic effects (n=5) were examined using mice bearing PC-12 as the in vivo study. Results MABG was highly taken up into PC-12 through the norepinephrine transporter (NET). Treatment with 0.2 kBq/mL MABG significantly suppressed the percent change of clonogenic growth compared to that in the controls (14.84 ± 4.43 %, P Conclusions MABG highly accumulated in PHEO cells via NET. MABG exhibited a strong therapeutic effect in a PHEO mice model without an associated weight reduction. Therefore, MABG might be an attractive therapeutic agent for the treatment of malignant PHEO.