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

Abstract

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 [123I]metomidate ([123I]IMTO) in ACC lesions, suggesting that labeling of metomidate with 131I offers targeted radionuclide therapy for advanced ACC. Safety and efficacy of radionuclide therapy with [131I]IMTO in advanced ACC. This monocentric case series comprised 19 treatments in 11 patients with nonresectable ACC. Between 2007 and 2010, patients with advanced ACC not amenable to radical surgery and exhibiting high uptake of [123I]IMTO in their tumor lesions were offered treatment with [131I]IMTO (1.6-20 GBq in one to three cycles of [131I]IMTO). 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). 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 [131I]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. Radionuclide therapy with [131I]IMTO is a promising treatment option for selected patients with ACC, deserving evaluation in prospective clinical trials.