[131I]Iodometomidate for Targeted Radionuclide Therapy of Advanced Adrenocortical Carcinoma

Context: In advanced adrenocortical carcinoma (ACC), many patients have progressive disease despite standard treatment, indicating a need for new treatment options. We have shown high and specific retention of [I-123]metomidate ([I-123]IMTO) in ACC lesions, suggesting that labeling of metomidate with I-131 offers targeted radionuclide therapy for advanced ACC. Objective: Safety and efficacy of radionuclide therapy with [I-131]IMTO in advanced ACC. Design/Setting: This monocentric case series comprised 19 treatments in 11 patients with nonresectable ACC. Patients and Intervention: Between 2007 and 2010, patients with advanced ACC not amenable to radical surgery and exhibiting high uptake of [I-123]IMTO in their tumor lesions were offered treatment with [I-131]IMTO (1.6-20 GBq in one to three cycles of [I-131]IMTO). Main Outcome Measure: Tumor response was assessed according to response evaluation criteria in solid tumors (RECIST version 1.1) criteria, and side effects were assessed by Common Toxicity Criteria (version 4.0). Results: Best response was classified as partial response in one case with a change in target lesions of -51% from baseline, as stable disease in five patients, and as progressive disease in four patients. One patient died 11 d after treatment with [I-131]IMTO unrelated to radionuclide therapy. In patients responding to treatment, median progression-free survival was 14 months (range, 5-33) with ongoing disease stabilization in three patients at last follow-up. Treatment was well tolerated, but transient bone marrow depression was observed. Adrenal insufficiency developed in two patients. Conclusions: Radionuclide therapy with [I-131]IMTO is a promising treatment option for selected patients with ACC, deserving evaluation in prospective clinical trials. (J Clin Endocrinol Metab 97: 914-922, 2012)