Radiation Dose Estimates for I-123 and I-131 MIBG, With Comparisons to Doses from External Beam Radiation

Objectives: I-131 m-iodo-benzylguanidine (MIBG, or Iobenguane) is a norepinephrine analog that has been widely used to treat relapsed or refractory neuroblastoma (NB), as well in a number of other neuroendocrine tumors, such as pheochromocytoma and paragangioma. While I-131 MIBG is approved as a radiotherapeutic agent in a number of countries, and has been previously approved as a radiodiagnostic agent in the U.S., it is not approved in the United States as a radiotherapeutic agent. The current review was designed to provide data necessary to demonstrate the radiation safety of I-131 MIBG as part of an evaluation of the safety and efficacy of I-131 MIBG as a radiotherapeutic agent for the treatment of subjects with iobenguane avid high-risk neuroblastoma at the time of first relapse following initial therapy. Importantly, MIBG for pediatric NB, because of the use of autologous stem cell transplant marrow rescue allows higher administered MIBG doses and the potential for curative or longer, more durable responses.

Methods: We revisited the published dosimetry models and dose estimates for I-123 and I-131 MIBG, using the OLINDA/EXM 1.1 software code. The recommended model of the ICRP for this agent, based on four literature sources, was employed for both isotopes of iodine, and for four possible dosing levels for I-131 MIBG. Results were compared to previously published dose estimates, as well as external beam dose estimates as may be employed for these diseases. RESULTS: Total body doses ranged from 0.91 to 3.78 Gy (91 to 378 rad) for persons of age 1 year to adult, assuming administration of 185, 370, 555, or 666 MBq (5, 10, 15, or 18 mCi) of I-131 MIBG/kg of body weight (at reference ages given in ICRP Publication 90 (2002)). This compares with somewhat higher values reported by Flux et al. (2011) of 1,540 to 33,000 MBq in eight published studies. We compared the total body doses (comparable to red marrow doses) to the TD(5/5) and TD(50/5) values cited by Meredith et al. (Semin Nucl Med 38:347-357, 2008), although no specific data on MIBG were included in their analysis. CONCLUSIONS: The standardized dosimetry for I-123 and I-131 MIBG is well established, based on the ICRP biokinetic model and the results from the OLINDA/EXM computer code. Radiation doses for actual patients will vary, based on the tumor type, individual biokinetics and body sizes, as well as the actual administered activities of I-131 MIBG. Our understanding of the biological effects for internally administered radionuclides continues to improve with expanded clinical applications for radiotherapeutic agents, such as I-131 MIBG.