Local delivery of (131)I-MIBG to treat peritoneal neuroblastoma

Internal radiotherapy involving systemic administration of iodine-131 metaiodobenzylguanidine ((131)I-MIBG) in neural crest tumours such as neuroblastoma has shown considerable success. Although peritoneal seeding of neuroblastoma occurs less often than metastases to organs such as the liver, no effective treatments exist in this clinical setting. Previous reports have demonstrated the effectiveness of peritoneal application of chemotherapeutic drugs or radiolabelled monoclonal antibodies in several kinds of carcinomas. Local delivery of (131)I-MIBG should produce more favourable dosimetry in comparison with its systemic administration in the treatment of peritoneal neuroblastoma. In the current investigation, a peritoneal model of neuroblastoma was established in Balb/c nu/nu mice by i.p. injection of SK-N-SH neuroblastoma cells. Two weeks after cell inoculation, comparative biodistribution studies were performed following i.v. or i.p. administration of (131)I-MIBG. Mice were treated with 55.5 MBq of (131)I-MIBG administered either i.v. or i.p. at 2 weeks. Intraperitoneal injection of (131)I-MIBG produced significantly higher tumour accumulation than did i.v. injection ( P<0.01). Therapeutic ratios of i.p. injection were 4- to 14-fold higher than those of i.v. injection. Radiotherapy with i.v. administered (131)I-MIBG failed to improve the survival of mice; mean survival of untreated mice and mice treated with i.v. administration of (131)I-MIBG was 59.3+/-3.9 days and 60.6+/-2.8 days, respectively. On the other hand, radiotherapy delivered via i.p. administration of (131)I-MIBG prolonged survival of mice to 94.7+/-17.5 days ( P<0.02 vs untreated controls and mice treated with i.v. (131)I-MIBG therapy). Radiation doses absorbed by tumours at 55.5 MBq of (131)I-MIBG were estimated to be 4,140 cGy with i.p. injection and 450 cGy with i.v. injection. These results indicate the benefits of locoregional delivery of (131)I-MIBG in the treatment of peritoneal neuroblastoma.