Targeting 11-Beta Hydroxylase With [I-131]IMAZA: A Novel Approach for the Treatment of Advanced Adrenocortical Carcinoma

Hahner, Stefanie; Hartrampf, Philipp E.; Mihatsch, Patrick W.; Nauerz, Marc; Heinze, Britta; Haenscheid, Heribert; Fuss, Carmina Teresa; Werner, Rudolf A.; Pamporaki, Christina; Kroiss, Matthias; Fassnacht, Martin; Buck, Andreas K. und Schirbel, Andreas (2022): Targeting 11-Beta Hydroxylase With [I-131]IMAZA: A Novel Approach for the Treatment of Advanced Adrenocortical Carcinoma. In: Journal of Clinical Endocrinology & Metabolism, Bd. 107, Nr. 4, E1348-E1355

Abstract

Context 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. Objective Here, we report a new theranostic approach to advanced ACC applying (R)-1-[1-(4-[I-123]iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinyl amide ([I-123]IMAZA) for diagnostic imaging and [I-131]IMAZA for radionuclide therapy. Methods Sixty-nine patients with nonresectable, metastatic ACCs were screened using a diagnostic [I-123]IMAZA scan. Patients with significant uptake in all tumoral lesions were offered treatment with [I-131]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 [I-131]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 2 patients. Five patients with disease stabilization experienced a median progression-free survival of 14.3 months (range 8.3-21.9). Median overall survival in all patients was 14.1 months (4.0-56.5) after therapy. Treatment was well tolerated, in other words no severe toxicities (CTCAE grade >= 3) were observed. Conclusion In patients with advanced ACC refractory to standard therapeutic regimens, [I-131]IMAZA treatment was associated with disease stabilization and nonsignificant tumor size reduction in a significant patient fraction and only limited toxicities. High [I-131]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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0021-972X
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 314061271