TY - JOUR T1 - <strong>Effects and safety of alpha-emitting meta-<sup>211</sup>At-astato-benzylguanidine (<sup>211</sup>At-MABG) compared with <sup>131</sup>I-meta-iodobenzylguanidine (<sup>131</sup>I-MIBG) on tumor growth suppression in a pheochromocytoma mouse model</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1316 LP - 1316 VL - 61 IS - supplement 1 AU - Songji Zhao AU - Keiichiro Yoshinaga AU - Komei Washino AU - Miho Aoki AU - Ken-ihi Nishijima AU - Saki Shimoyama AU - Naoyuki Ukon AU - Fengying Gao AU - Kohshin Washiyama AU - Natsue Ito AU - Naho Yoshioka AU - Naomi Tamura AU - Kazuhiro Takahashi AU - Tatsuya Higashi AU - Hiroshi Ito Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/1316.abstract N2 - 1316Objectives: Given the limited treatment approaches currently available for patients with metastatic pheochromocytoma and paraganglioma (PPGL), new effective approaches are being sought. The radioisotope approach using 131I-meta-iodobenzylguanidine (131I-MIBG) has limited survival benefits in metastatic PPGL but is currently considered one of the standard therapeutic approaches. In theory, the alpha-emitting radiopharmaceutical meta-211At-astato-benzylguanidine (211At-MABG) could be a very effective targeted treatment for metastatic PPGL with few side effects. However, its possible therapeutic effects and safety have not been evaluated. Therefore, the purpose of the current study was to evaluate the tumor growth suppression effects and safety aspects of 211At-MABG compared to 131I-MIBG using a PC-12 mouse pheochromocytoma model. Methods: Rat pheochromocytoma (PC-12) cells were subcutaneously inoculated into male BALB/c nu/nu nude mice. When tumor volumes reached approximately 300 mm3, mice bearing PC-12 tumors received intravenously either 1.11 MBq of 211At-MABG (n=6), 31 MBq of 131I-MIBG (n=3) or vehicle solvent (n = 6). The tumor volume was measured 3 times per week for 2 weeks. The tumor volumes were compared among the three groups. In terms of safety aspects, we measured body weight change 3 times per week and observed findings of dry skin and diarrhea every day in both the 211At-MABG and 131I-MIBG groups. Results: At 14 days, the tumor volumes significantly increased in the control group (328.82±83.65 to 3568.83±693.23 mm3, P&lt;0.001). In contrast, there were no significant changes in tumor volumes in the 211At-MABG group (284.65±56.77 to 274.3±87.95 mm3, P=0.616) and 131I-MIBG group (484.40±46.25 to 323.93±127.27 mm3, P=0.084). The 211At-MABG group showed significantly lower percentage change in tumor volume than did the control group (-5.0±15.99 vs 1043.83±320.79%, P&lt;0.001), and the 131I-MIBG group also showed a significant volume reduction rate compared to that of the control group (-34.33±21.39 vs 1043.82±320.79%, P&lt;0.001). There was no significant difference in percentage tumor volume changes between the 211At-MABG and 131I-MIBG groups (P=0.052). There were no significant differences in body weights among 3 groups (22.50±0.91g for control, 23.25±0.60g for 211At-MABG and 23.00±0.80g for 131I-MIBG; P=NS) before the treatment. There were no significant differences in body weights between pretreatment and 14 days after the treatment in the two treatment groups (23.25±0.60g vs 23.12±0.81g for 211At-MABG; P=0.5047 and 23.00±0.80g vs 22.6±0.53g for 131I-MIBG; P=0.3001), while mild reductions in mouse body weights were observed both in 211At-MABG and 131I-MIBG groups. The body weight changes were similar and there was no significant difference in percent change between the 211At-MABG and 131I-MIBG groups (-0.58±1.98% vs -1.70±2.10%, P=0.538). There were no observed findings of dry skin or diarrhea after the treatment with 211At-MABG or 131I-MIBG. Conclusion: At 14 days after radiopharmaceutical administration, 211At-MABG produced significant tumor volume reduction as compared to that in the control group. 211At-MABG had a tumor-reducing effect similar to that associated with 131I-MIBG, which is considered one of the current treatment options. There was also no significant difference in body weight change between pretreatment and 14 days after treatment with 211At-MABG and 131I-MIBG. No obvious evidence of toxicity was observed in either the 211At-MABG or 131I-MIBG group. Therefore, 211At-MABG may be an effective targeted treatment without obvious side effects for metastatic PPGL, and 211At-MABG may have future clinical applications for the treatment of metastatic pheochromocytoma and paraganglioma. ER -