Effects and safety of alpha-emitting meta-211At-astato-benzylguanidine (211At-MABG) compared with 131I-meta-iodobenzylguanidine (131I-MIBG) on tumor growth suppression in a pheochromocytoma mouse model

1316 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 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