A Phase I/IIa Clinical Trial to Evaluate Safety and Adrenal Uptake of Para-Chloro-2-[18F]Fluoroethyletomidate in Healthy Volunteers and Patients with Primary Aldosteronism.

Abstract

Primary aldosteronism (PA) is a common, potentially reversible, cause of hypertension. Distinguishing unilateral from bilateral PA is critical when deciding who should be offered surgery (unilateral adrenalectomy). Recent studies have shown that PET/CT with [¹¹C]metomidate can accurately identify unilateral PA, with localization of the causative aldosterone-producing adenoma (APA). However, the availability of [¹¹C]metomidate is limited to centers with an on-site cyclotron. Here, we report an early-phase human study with the ¹⁸F-labeled analog, para-chloro-2-[¹⁸F]fluoroethyletomidate ([¹⁸F]CETO). Methods: We conducted a phase I/IIa, single-center, open-label, microdosing study. The primary objective was to evaluate the safety of up to 2 administrations of [¹⁸F]CETO in 6 patients with PA (3 unilateral disease, 3 bilateral disease) and 5 healthy volunteers. Safety evaluation included assessment of adrenal function after the first [¹⁸F]CETO administration. The biodistribution of [¹⁸F]CETO was assessed in a 90-min dynamic PET acquisition. In patients with PA, the effect of pretreatment with oral dexamethasone on [¹⁸F]CETO uptake by normal adrenal tissue and APAs was also assessed. Results: Eleven participants were recruited to the trial, including 6 patients and 5 healthy volunteers. No subjects experienced serious adverse events or reactions, and all participants had normal adrenal function after [¹⁸F]CETO administration. [¹⁸F]CETO demonstrated high selectivity for the adrenal glands with low uptake in other tissues. Visualization of APAs was enhanced after dexamethasone pretreatment, which suppressed [¹⁸F]CETO uptake by normal adrenal tissue. Conclusion: [¹⁸F]CETO is a safe radiopharmaceutical for PET imaging of the adrenal glands, with no observed adverse reactions or impairment of adrenal function in this study. [¹⁸F]CETO demonstrates selective high affinity for adrenal tissue, particularly APAs. Distinction between APAs and normal adrenal tissue is enhanced by dexamethasone pretreatment to suppress [¹⁸F]CETO uptake by normal glands. This positions [¹⁸F]CETO as a promising imaging tool for evaluation in the context of PA.