First-in-human evaluation of [18F]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