Efficacy and safety of 124 I-mIBG dosimetry-guided high activity 131 I-mIBG therapy of advanced pheochromocytoma or neuroblastoma.

Introduction: We aim to evaluate the efficacy and safety of 124 I-mIBG dosimetry guided high-activity 131 I-mIBG therapy of advanced pheochromocytoma or neuroblastoma. Methods: Fourteen patients with advanced pheochromocytoma or neuroblastoma, age 9 to 69 years, underwent 124 I-mIBG PET scans and whole-body retention measurements to assess the whole-body dose as a surrogate of bone marrow toxicity and tumor (absorbed) dose per unit of administered activity. Dosimetry results together with individual patient characteristics were combined to guide a single therapeutic activity to achieve a high tumor dose without exceeding toxicity threshold. Toxicity was assessed for hematologic, hepatic as well as renal function. Response was evaluated by RECIST, SIOPEN-like score, change in PET uptake and quantitative PET parameters (SUVmax , SUVpeak, MTV, TLG) as well as visual decrease in number and/or in visual intensity of lesions on baseline to follow-up 124 I-mIBG-PET/CT. Results: The mean therapeutic activity was 14 GBq. Eleven of 14 patients (79%) received each more than 10 GBq. One male patient was treated with a single activity of 50 GBq. Three patients were treated with lower activities between 3.5 and 7.0 GBq. Median overall survival was 85 months (95% CI), median progression-free survival was 25 months (95% CI). Four (29%) and 5 (36%) patients demonstrated response (CR or PR) by RECIST and functional imaging, respectively. One patient exceeded whole-body dose of 2 Gy and demonstrated grade 3 hematologic toxicity, which resolved spontaneously within 12 months after the therapy without the need for further treatment. Three patients (21%) demonstrated transient grade 1 renal toxicity. Conclusion: 124 I-mIBG dosimetry-guided high-activity 131 I-mIBG therapy in patients with advanced pheochromocytoma or neuroblastoma resulted in durable responses with a low rate of manageable adverse events. Efficacy of 124 I-mIBG-guided activity escalation should further be assessed in a prospective setting.