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.
Interventions Participating patients have been subjected to the routine diagnostic
work-up for PA as recommended by the guideline of the European Society of Hypertension
(2020), including hormonal evaluation before and after a salt-loading protocol, CT or MRI
of the adrenal glands and AVS. Three days prior to the PET/CT scans, patients receive
pretreatment with dexamethasone in order to enhance tracer specificity. Each participant
will be subjected to one additional hospital visit for the investigational diagnostic
PET-CT procedure with the administration of [18F]CETO, which is directly preceded by a
15O water scan.
Ethical considerations relating to the clinical trial including the expected benefit to
the individual subject or group of patients represented by the trial subjects as well as
the nature and extent of burden and risks.
No adverse effects following [18F]CETO and 15O water injection have been reported in the
literature. Pretreatment with dexamethasone is recommended for the [18F]CETO PET/CT and
could result in mild reversible side effects (hyperglycemia, mood changes, sleep
disturbance), which will be monitored by means of a non-invasive questionnaire. As this
is a diagnostic pilot study, participating patients will not benefit directly from this
investigational diagnostic procedure. However, patients contribute to gathering
information on the application of [18F]CETO PET/CT, potentially reducing the need for AVS
in future patients.