OR03-01 Effects Of Alpha-emitting Meta-211At-astato-benzylguanidine (211At-MABG) Compared To 131I-meta-iodobenzylguanidine (131I-MIBG) on Tumor Growth Suppression in a Pheochromocytoma Mouse Model

Abstract Objectives: 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. However, this possibility has not been evaluated. Therefore, the purpose of this study was to evaluate the tumor growth suppression effects 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 volume was compared among the three 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<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<0.001), and 131I-MIBG group also showed significant volume reduction rate compared to that of the control group (-34.33±21.39 vs. 1043.82±320.79%, P<0.001). There was no significant difference in percentage tumor volume changes between the 211At-MABG and 131I-MIBG groups (P=0.052). Conclusion: At 14 days after radiopharmaceutical administration, 211At-MABG produced significant tumor volume reduction as compared to that in the control group and to that associated with 131I-MIBG, which is considered one of the current treatment options. Therefore, 211At-MABG may have future clinical applications for the treatment of metastatic pheochromocytoma and paraganglioma.