Targeting 11-beta hydroxylase with [ 131I]IMAZA – a novel approach for the treatment of advanced adrenocortical carcinoma
Abstract Introduction Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options. Theranostic approaches with adrenal specific radiotracers hold promise for improved diagnostics and treatment. Here, we report a new theranostic approach to advanced ACC applying (R)-1-[1-(4-[ 123I]Iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinyl amide ([ 123I]IMAZA) for diagnostic imaging and [ 131I]IMAZA for radionuclide therapy. Patients and treatment 69 patients with non-resectable, metastatic ACC were screened, using a diagnostic [ 123I]IMAZA scan. Patients with significant uptake in all tumoral lesions were offered treatment with [ 131I]IMAZA. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1), and adverse effects were assessed by Common Toxicity Criteria (version 5.0). Results After screening, 13 patients were treated with a median of 25.7 GBq [ 131I]IMAZA (range, 18.1–30.7 GBq). Five individuals received a second treatment course. Best response was a decrease in the RECIST target lesions of 26% in two patients. Five patients with disease stabilization experienced a median progression-free survival of 14.3 months (range, 8.321.9). Median overall survival in all patients was 14.1 months (4.056.5) after therapy. Treatment was well tolerated, i.e. no severe toxicities (CTCAE grade ≥3) were observed. Conclusion In patients with advanced ACC refractory to standard therapeutic regimens, [ 131I]IMAZA treatment was associated with disease stabilization and non-significant tumour size reduction in a significant patient fraction and only limited toxicities. High [ 131I]IMAZA-uptake in tumor lesions was observed in 38.5% of patients with advanced ACC, rendering [131I] IMAZA a potential treatment option in a limited, well-defined patient fraction. Further clinical trials will be necessary to evaluate the full potential of this novel theranostic approach.