Abstract
Neuroblastoma, which derives from neural crest, is the most common extracranial solid cancer in childhood. The tumors express the norepinephrine (NE) transporters on their cell membrane and take in metaiodobenzylguanidine (MIBG) via a NE transporter. Since iodine-131 (I-131) MIBG therapy was firstly reported, many trails of MIBG therapy in patients with neuroblastoma were performed. Though monotherapy with a low dose of I-131 MIBG could achieve high-probability pain reduction, the objective response was poor. In contrast, more than 12 mCi/kg I-131 MIBG administrations with or without hematopoietic cell transplantation (HCT) obtain relatively good responses in patients with refractory or relapsed neuroblastoma. The combination therapy with I-131 MIBG and other modalities such as nonmyeloablative chemotherapy and myeloablative chemotherapy with HCT improved the therapeutic response in patients with refractory or relapsed neuroblastoma. In addition, I-131 MIBG therapy incorporated in the induction therapy was proved to be feasible in patients with newly diagnosed neuroblastoma. To expand more the use of MIBG therapy for neuroblastoma, further studies will be needed especially in the use at an earlier stage from diagnosis, in the use with other radionuclide formations of MIBG, and in combined use with other therapeutic agents.
Highlights
Neuroblastoma derives from neural-crest tissues and arises mostly from adrenal medulla or paraspinal ganglia
In a phase I study from UCSF, 30 patients with refractory or relapsed neuroblastoma were treated with I-131 MIBG at escalating doses of 3 to 18 mCi/kg per each therapy [28]
In a phase I study from the new approaches to neuroblastoma therapy (NANT) consortium, 24 patients with refractory or relapsed neuroblastoma treated with irinotecan which is another topoisomerase I inhibitor, vincristine, and I-131 MIBG at escalating doses of 8 to 18 mCi/kg [48]
Summary
Neuroblastoma derives from neural-crest tissues and arises mostly from adrenal medulla or paraspinal ganglia. More than one-third of the patients are diagnosed younger than one-year-old and the median age at diagnosis is 17 months [2]. Age greater than 12 or 18 months at diagnosis and patients with an advanced primary lesion or metastases and patients with MYCN amplification have worse outcomes [2,3,4]. Since metaiodobenzylguanidine (MIBG) was reported as the adrenomedullary imaging agent in the early 1980s [6,7,8], iodine-131 (I-131) MIBG and iodine-123 (I-123) MIBG were widely used for detecting neuroendocrine tumors such as pheochromocytoma, neuroblastoma, and medullary thyroid cancer [9]. We detail the development of I-131 MIBG therapy in patients with neuroblastoma from the last decades to the future
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