9011 Background: 131I-MIBG provides targeted radiotherapy with >30% response in refractory neuroblastoma, but the activity infused is limited by radiation safety and hematologic toxicity. The goal was to determine the maximum tolerated dose of 131I-MIBG in two consecutive infusions at a 2-week interval, supported by autologous stem cell transplant (ASCT) 2 weeks after the second dose. Methods: The 131I-MIBG was escalated in a 3+3 Phase I trial design, with levels calculated by total red marrow radiation index (RMI) from the double infusion. The first infusion of 131I-MIBG was 12, 15, 18 and 21 mCi/kg for levels 1, 2, 3 and 4 respectively. Using detailed dosimetry, the second infusion was adjusted to achieve the target RMI, except at Level 4, where the second infusion was capped at 21 mCi/kg. Results: Twenty-one patients were enrolled at Level 1–4, with 18 evaluable for toxicity. Median age at enrollment was 7 years, all were heavily pretreated, including 12 with prior high dose therapy and ASCT, and 12 patients had bone marrow tumor. Cumulative 131I-MIBG given to achieve the target RMI ranged from 18 mci/kg to 49 mCi/kg. RMI delivered per mCi of MIBG decreased in 15/19 patients by mean of 0.21 cGy/mCi with the second infusion. Hematologic toxicity was acceptable, with median time to ANC>500 after ASCT of 13 (4–27) days. Platelet transfusion was required in 15/18 patients, with median time to platelet independence of 18 (6–47) days after ASCT. There were no non-hematologic toxicities above grade 2 attributed to therapy, though 9 patients had grade 1–2 elevations of transaminase, and 1 had grade 2 hypothyroidism. Responses in 17 evaluable patients included 1 PR, 4 MR, 6 SD, and 6 PD. Eleven patients are alive at median of 361 days (46–483); 5 died of PD and 1 of unrelated toxicity. Conclusion: The lack of toxicity with this approach allowed dramatic dose intensification of 131I-MIBG, with minimal toxicity and the possibility of improved response. [Table: see text] No significant financial relationships to disclose.