18F-CETO in Adrenocortical Carcinoma: First Clinical-Translational Study of An Adrenocortical-targeting PET Tracer
Adam Edholm, Liang Zhang, James MacFarlane, Tobias Åkerström, Russell Senanayake, Staffan Welin, Agnes Hegedus, Heok K. Cheow, Ieva Lase, Peter Stålberg, Azita Monazzam, Daniel Gillett, Luigi Aloj, Per Hellman, Hanna Wargelius, John A. Tadross, Gunnar Antoni, Franklin Aigbirhio, Britt Skogseid, Mark Gurnell, Samuel Backman, Anders Sundin, Ruth T. Casey, Joakim CronaAbstract
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.