A narrative review of 35 years of meta-[¹³¹I]iodobenzylguanidine therapy in neuroblastoma

Neuroblastoma is the most common extracranial solid malignancy of childhood. Approximately half of the patients have high-risk neuroblastoma (HR-NBL), typically presenting as widespread metastatic disease at diagnosis. Despite aggressive multimodality treatment, patients with HR-NBL have a long-term survival rate of below 50%. This is primarily due to frequent progression and relapse, which often proves to be therapy resistant. To overcome therapy resistance in HR-NBL, researchers are exploring diverse treatment strategies, including radionuclide therapy. Radiolabelled meta-iodobenzylguanidine (mIBG) has served as a theranostic (therapeutic and diagnostic) radiopharmaceutical in the field of neuroblastoma for several decades. [¹²³I]mIBG scintigraphy is recognized as the international standard to evaluate disease dissemination at diagnosis and to monitor treatment response. In contrast, the role of [¹³¹I]mIBG therapy in the management of neuroblastoma is less clear. Over the past 35 years, [¹³¹I]mIBG therapy has been studied in more than 1500 patients with neuroblastoma. In initial studies, [¹³¹I]mIBG monotherapy was applied as a second-line treatment in patients who failed first-line treatment. In current applications, [¹³¹I]mIBG therapy is combined with chemotherapy, radiosensitizers, and/or immunotherapy, and is increasingly integrated in the first-line treatment of HR-NBL. This narrative review provides an overview of the literature on [¹³¹I]mIBG therapy in HR-NBL. Studies show that [¹³¹I]mIBG therapy can be an effective treatment in one-third of patients with acceptable toxicity. Further investigations, particularly randomized controlled trials, are needed to determine the efficacy and optimal use of [¹³¹I]mIBG therapy in HR-NBL.