CXCR4-directed [⁶⁸Ga]Ga-PentixaFor PET/CT versus adrenal vein sampling performance: a study protocol for a randomised two-step controlled diagnoStic Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS)

Abstract

IntroductionPrimary aldosteronism (PA) is the most common form of secondary hypertension. It is caused by overproduction of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction is crucial, because PA is cured by adrenalectomy in APA and is treated by mineralocorticoid receptor antagonists in BAH. The distinction is currently made by adrenal vein sampling (AVS). AVS is a costly, invasive and complex technical procedure with limited availability and is not superior in terms of outcomes to CT scan-based diagnosis. Thus, there is a need for a cheaper, non-invasive and readily available diagnostic tool in PA. We propose a new diagnostic imaging modality employing the positron emission tomography (PET) tracer [68Ga]Ga-PentixaFor. This tracer has high focal uptake in APAs, whereas low uptake was shown in patients with normal adrenals. Thus, [68Ga]Ga-PentixaFor PET/CT is an imaging modality with the potential to improve subtyping of PA. It is readily available, safe and, as an out-patient procedure, much cheaper diagnostic method than AVS.Methods and analysisWe present a two-step randomised controlled trial (RCT) protocol in which we assess the accuracy of [68Ga]Ga-PentixaFor PET/CT in the first step and compare [68Ga]Ga-PentixaFor PET/CT to AVS in the second step. In the first step, the concordance will be determined between [68Ga]Ga-PentixaFor PET/CT and AVS and a concordance probability is calculated with a Bayesian prediction model. In the second step, we will compare [68Ga]Ga-PentixaFor PET/CT and AVS for clinical outcome and intensity of hypertensive drug use defined as daily defined doses in a RCT.Ethics and disseminationEthics approval was acquired from the medical ethical committee East-Netherlands (METC Oost-Nederland). Results will be disseminated through peer-reviewed articles.Trial registration numberNL9625.

Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks

“…An upcoming 2-step randomized control trial (CASTUS) will assess (1) The accuracy of 68 Ga-pentixafor PET/CT by determining the concordance between 68 Ga-Pentixafor PET/CT and AVS. If found to meet the predefined concordance threshold, the study will progress to assess (2) the clinical outcome in a randomized controlled trial of 68 Ga-Pentixafor PET/CT vs AVS with the primary outcome being the daily defined doses of antihypertensive drugs for BP regulation after 1 year, and secondary outcomes being quality of life, biochemical, and clinical cure (according to the PASO criteria) and costs ( 158 ). While current data highlight promising lateralization ability of 68 Ga-Pentixafor PET/CT, this tracer is not widely available for routine clinical use for patients with PA at this time.…”

Adrenal incidentalomas: unresolved diagnostic issues

“…Пациентам с подозрением на ПГА проводилось [ 68 Ga] Ga-PentixaForПЭТКТ, и было обнаружено повышенное очаговое поглощение препарата альдостеронпродуцирующей аденомой, тогда как существенно более низкое поглощение имело место у пациентов с нефункционирующей аденомой. Опираясь на эти данные, авторы поставили задачу определить значение [ 68 Ga]Ga-PentixaForПЭТКТ для верификации гормонпродуцирующего надпочечника у пациентов с двусторонней ПГА [37].…”