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

Abstract

[¹¹C]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 [¹¹C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[¹⁸F]fluoroethyletomidate has been proven to be a specific adrenal tracer. The objective is to perform a first evaluation of para-chloro-2-[¹⁸F]fluoroethyletomidate positron emission computed tomography ([¹⁸F]CETO-PET/CT) in patients with adrenal tumours and healthy volunteers. Fifteen patients underwent [¹⁸F]CETO-PET/CT. Five healthy volunteers were recruited for test-retest analysis and three out of the five underwent additional [¹⁵O]water PET/CT to measure adrenal blood flow. Arterial blood sampling and tracer metabolite analysis was performed. The kinetics of [¹⁸F]CETO were assessed and simplified quantitative methods were validated by comparison to outcome measures of tracer kinetic analysis. Uptake of [¹⁸F]CETO was low in the liver and high in adrenals. Initial metabolization was rapid, followed by a plateau. The kinetics of [¹⁸F]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 K₁. Both K₁ and SUV were highly correlated to adrenal blood flow in healthy controls. Repeatability coefficients of K₁, SUV_65-70, and SUV₁₂₀ were 25, 22, and 17%. High adrenal uptake combined with a low unspecific liver uptake suggests that ¹⁸F]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. ClinicalTrials.gov , NCT05361083 Retrospectively registered 29 April 2022. at,  https://clinicaltrials.gov/ct2/show/NCT05361083.