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Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
Published on: January 29, 2019
[131I]iodometomidate for targeted radionuclide therapy of advanced adrenocortical carcinoma
Stefanie Hahner1, Michael C Kreissl, Martin Fassnacht
1Endocrinology and Diabetes Unit, Department of Medicine I, University of Wuerzburg, Oberduerrbacher Strasse 6, D-97080 Wuerzburg, Germany.
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 [123I]metomidate ([123I]IMTO) in ACC lesions, suggesting that labeling of metomidate with 131I offers targeted radionuclide therapy for advanced ACC.
Objective:
Safety and efficacy of radionuclide therapy with [131I]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 [123I]IMTO in their tumor lesions were offered treatment with [131I]IMTO (1.6-20 GBq in one to three cycles of [131I]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 [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.
Conclusions:
Radionuclide therapy with [131I]IMTO is a promising treatment option for selected patients with ACC, deserving evaluation in prospective clinical trials.

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