Clinical applications and future directions of Iodine-131-Metaiodobenzylguanidine therapy in neuroblastoma: from salvage treatment to frontline integration

Neuroblastoma is the most common extracranial solid tumor in children and often requires complex, multimodal treatment. A major advancement in its treatment has been the development of metaiodobenzylguanidine (MIBG), a norepinephrine analog, for diagnostic imaging and targeted radiotherapy. This review provides a comprehensive overview of the clinical applications and recent advancements of 131I-MIBG in neuroblastoma treatment. The agent has exhibited substantial efficacy in newly diagnosed and relapsed or refractory disease, through strategies such as monotherapy, tandem dosing, and high-dose administration with stem cell transplantation support. Combination regimens incorporating radiosensitizers, chemotherapeutic agents, and novel targeted approaches-including histone deacetylase inhibitors and immunotherapy-have further broadened its therapeutic scope. Challenges remain, including nonavid tumors, radiation-related risks, and logistical constraints. However, with the recent regulatory approval of 131I-MIBG for neuroblastoma treatment in Japan, its role is expected to expand, paving the way for improved outcomes and more personalized, targeted approaches in pediatric oncology.