Radiolabeled metaiodobenzylguanidine for the treatment of neuroblastoma

Abstract

Introduction Neuroblastoma is the most common pediatric extracranial solid cancer. This tumor is characterized by metaiodobenzylguanidine (MIBG) avidity in 90% of cases, prompting the use of radiolabeled MIBG for targeted radiotherapy in these tumors. Methods The available English language literature was reviewed for original research investigating in vitro, in vivo, and clinical applications of radiolabeled MIBG for neuroblastoma. Results MIBG is actively transported into neuroblastoma cells by the norepinephrine transporter. Preclinical studies demonstrate substantial activity of radiolabeled MIBG in neuroblastoma models, with 131I-MIBG showing enhanced activity in larger tumors compared to 125I-MIBG. Clinical studies of 131I-MIBG in patients with relapsed or refractory neuroblastoma have identified myelosuppression as the main dose-limiting toxicity, necessitating stem cell reinfusion at higher doses. Most studies report a response rate of 30–40% with 131I-MIBG in this population. More recent studies have focused on the use of 131I-MIBG in combination with chemotherapy or myeloablative regimens. Conclusions 131I-MIBG is an active agent for the treatment of patients with neuroblastoma. Future studies will need to define the optimal role of this targeted radiopharmaceutical in the therapy of this disease.

Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with 131I‐metaiodobenzylguanidine with implications for the activity to administer

“…During the last two decades several studies have been published on the use of 131 I-mIBG for NB and NET treatments [5][6][7][8][9][10][11][12] , and guidelines have been provided by the European Association of Nuclear Medicine (EANM) 4 . The administered activity is most commonly prescribed using 60 3 fixed activities 13,14 or a specified activity per patient mass [15][16][17][18] or per body surface 19 .…”

Dose Escalation Study of No-Carrier-Added 131I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

“…MIBG is specifically concentrated in 90% of neuroblastoma and is an essential component of staging when labeled with 123 I (4). MIBG labeled with 131 I provides tumor-specific radiation and has been shown to be one of the most active therapies for relapsed neuroblastoma, with a 20%-37% response rate (5)(6)(7)(8). Phase 1 and 2 studies suggest a dose response, and therefore patients have been treated with higher amounts of 131 I-MIBG supported with autologous peripheral blood stem cell transplantation (ASCT) to prevent toxicity from the myelosuppressive effects of radiation (8)(9)(10).…”

Recurrent Neuroblastoma

“…131 I-MIBG therapy is generally well tolerated, except for myelosuppression that may require stem cell support in heavily pretreated patients (DuBois et al, 2004). MIBG monotherapy achieved responses in up to a third of relapsed patients at doses 12 mCi/kg, but with no long-term cure (DuBois & Matthay, 2008). In a large phase II trial of 164 patients receiving 12 to 18 mCi/kg of 131 I-MIBG, the overall response rate was 36% and SD rate was 36%, and the 2-year OS was 29% (Matthay et al, 2007).…”