First-in-human evaluation of [(18)F]CETO: a novel tracer for adrenocortical tumours

PURPOSE: [(11)C]Metomidate positron emission tomography (PET) is currently used for staging of adrenocortical carcinoma and for lateralization in primary aldosteronism (PA). Due to the short half-life of carbon-11 and a high non-specific liver uptake of [(11)C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[(18)F]fluoroethyletomidate has been proven to be a specific adrenal tracer. The objective is to perform a first evaluation of para-chloro-2-[(18)F]fluoroethyletomidate positron emission computed tomography ([(18)F]CETO-PET/CT) in patients with adrenal tumours and healthy volunteers. METHODS: Fifteen patients underwent [(18)F]CETO-PET/CT. Five healthy volunteers were recruited for test-retest analysis and three out of the five underwent additional [(15)O]water PET/CT to measure adrenal blood flow. Arterial blood sampling and tracer metabolite analysis was performed. The kinetics of [(18)F]CETO were assessed and simplified quantitative methods were validated by comparison to outcome measures of tracer kinetic analysis. RESULTS: Uptake of [(18)F]CETO was low in the liver and high in adrenals. Initial metabolization was rapid, followed by a plateau. The kinetics of [(18)F]CETO in healthy adrenals and all adrenal pathologies, except for adrenocortical carcinoma, were best described by an irreversible single-tissue compartment model. Standardized uptake values (SUV) correlated well with the uptake rate constant K(1). Both K(1) and SUV were highly correlated to adrenal blood flow in healthy controls. Repeatability coefficients of K(1), SUV(65–70), and SUV(120) were 25, 22, and 17%. CONCLUSIONS: High adrenal uptake combined with a low unspecific liver uptake suggests that (18)F]CETO is a suitable tracer for adrenal imaging. Adrenal SUV, based on a whole-body scan at 1 h p.i., correlated well with the net uptake rate K(i). TRIAL REGISTRATION: ClinicalTrials.gov, NCT05361083 Retrospectively registered 29 April 2022. at, https://clinicaltrials.gov/ct2/show/NCT05361083 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-022-05957-9.