PT - JOURNAL ARTICLE AU - Yasuhiro Ohshima AU - Shigeki Watanabe AU - Atsushi Tsuji AU - Kotaro Nagatsu AU - Tetsuya Sakashita AU - Akira Sugiyama AU - Yoshinobu Harada AU - Atsuo Waki AU - Keiichiro Yoshinaga AU - Noriko Ishioka TI - Therapeutic efficacy of α-emitter meta-211At-astato-benzylguanidine (MABG) in a pheochromocytoma model DP - 2016 May 01 TA - Journal of Nuclear Medicine PG - 468--468 VI - 57 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/57/supplement_2/468.short 4100 - http://jnm.snmjournals.org/content/57/supplement_2/468.full SO - J Nucl Med2016 May 01; 57 AB - 468Objectives 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<0.0001), and induced cell death in PC-12. DNA damage and cell cycle arrest at the G2/M phase were observed after MABG treatment. MABG was highly distributed and was retained in tumors (36.21 ± 16.74 %ID/g at 3 h, 16.43 ± 5.69 %ID/g at 24 h post-injection). Furthermore, the tumor size was significantly reduced by the single administration of MABG (555 kBq/head) compared to the case for the control group at 7 days after MABG administration (relative value to the initial tumor volume: 0.54 ± 0.12 (MABG) vs.1.82 ± 0.60 (control), P<0.01). The MABG treatment group did not show any weight reduction compared to the control group at day 7 (P=0.881).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.