Subtyping Primary Aldosteronism With Para-chloro-2-[18F]Fluoroethyl-etomidate

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?secondary objective An additional result the study measures alongside the primary outcome, for example quality of life or a laboratory value. 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?endpoints Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory. 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?observational A study in which researchers do not assign participants to a treatment or other intervention. They observe or measure what happens, which may include study visits, tests, questionnaires or a review of medical records. 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?exclusion criteria The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy. 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?CT An X-ray scan that builds detailed cross-section images of the body. 'High-resolution' CT (HRCT) is used to look closely at the lungs. or MRI?MRI A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one. 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?investigational A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study. 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.