Para-chloro-2-[18F]fluoroethyl-etomidate ([18F]CETO) As a New PET-tracer for Subtyping in Patients with Primary Aldosteronism - a Pilot Study

Rationale Primary aldosteronism (PA) is a relatively frequent and clinically relevant secondary cause of hypertension. PA is usually caused by either an aldosterone producing adrenal adenoma (APA) or bilateral adrenal hyperplasia (BAH). Differentiation between these two subtypes is important as it determines the treatment of choice, i.e., unilateral adrenalectomy in case of APA and medical treatment with a mineralocorticoid receptor antagonist in case of BAH. Adrenal vein sampling (AVS) is considered the optimal diagnostic test for this subtyping and is recommended in most patients with PA who are a candidate for surgery. AVS, however, is an invasive and time-consuming procedure with limited availability due to the special expertise required. Additional disadvantages are the risk of procedure related complications and the relative high costs. Thus, there is an unmet need for a non-invasive, faster, more patient friendly and less expensive diagnostic test which can distinguish between the two main subtypes of PA. PET/CT with para-chloro-2-[18F]fluoroethyl-etomidate ([18F]CETO) has a high specificity for the steroidogenic enzymes CYP11B1 and CYP11B2, present in the adrenal cortex, and has more favourable tracer characteristics compared to [11C]metomidate. Results obtained with this novel tracer seem promising, but its potential value in the subtyping of PA needs to be further established. Our hypothesis is that [18F]CETO PET/CT is selectively taken up by aldosterone producing adrenal tissue.

Objective The main objective is to investigate the uptake characteristics of [18F]CETO in adrenal tissue in patients with either APA or BAH. The secondary objective is to evaluate the concordance between the results of adrenal vein sampling and the results of the [18F]CETO scan. In addition, the effect of tissue perfusion on the [18F]CETO uptake by means of a 15O water scan is studied.

Main trial endpoints The main trial endpoint is the investigation of [18F]CETO uptake by adrenal gland tissue in patients with either APA or BAH. Descriptive statistics will be used to explore uptake characteristics.

Secondary trial endpoints The secondary trial end points are i) the concordance between the results of adrenal vein sampling and ii) the relationship between adrenal perfusion and [18F]CETO uptake Trial design Prospective, single-center, diagnostic, observational pilot study. The expected duration of this study is 2 years.

Trial population Adult patients > 18 years of age with biochemically confirmed PA who underwent a successful AVS (n=12) are eligible for inclusion. Main exclusion criteria are diabetes mellitus, serious comorbidity precluding surgery and use of specific medications.