18F-CETO in Adrenocortical Carcinoma: First Clinical-Translational Study of An Adrenocortical-targeting PET Tracer

The adrenocortical-specific PET-tracer [11C]metomidate (11C-MTO) shows high diagnostic accuracy in adrenocortical carcinoma (ACC), but complex radiochemistry and short half-life limit clinical implementation. The novel tracer para-chloro-2-[18F]fluoroethyletomidate (18F-CETO) may enable broader use. In this bicentric study, 20 ACC patients underwent PET/CT with 18F-CETO and 18F-FDG with 235 lesions identified. 18F-CETO detected more lesions than 18F-FDG at initial staging in 5/13 patients, whereas fewer lesions were detected at restaging in 5/7 patients (p=0.002). A further 70 patients with 18F-CETO or 11C-MTO-PET/CT and an anatomical imaging reference was used to explore the utility of adrenocortical imaging. Three adrenocortical imaging phenotypes were defined: homogeneous-high (n=71), homogeneous-low (n=11) and heterogeneous (n=8), which showed differences in overall survival in exploratory analyses.Tumors were characterized by RNA sequencing and immunohistochemistry showing correlation between tracer-uptake to CYP11B1 expression and adrenocortical differentiation. These findings suggest a potential role for 18F-CETO in ACC phenotyping and initial staging.