Diagnostic concordance of CXCR4-PET/CT and adrenal vein sampling in subtyping primary aldosteronism and its guiding value for percutaneous adrenal artery embolisation: a prospective diagnostic test accuracy study protocol

Introduction Primary aldosteronism (PA) is the most common cause of secondary hypertension, and accurate differentiation between unilateral and bilateral disease is critical for selecting appropriate therapy. In patients undergoing adrenalectomy, histopathological classification based on the International Histopathology Consensus for Unilateral Primary Aldosteronism provides a definitive reference for unilateral disease. Although adrenal vein sampling (AVS) remains the diagnostic gold standard, it is invasive, technically demanding and often limited by variable success rates. CXCR4-targeted positron emission tomography (CXCR4-PET)/CT has emerged as a promising non-invasive imaging modality capable of identifying aldosterone-producing lesions, but robust prospective evidence comparing it directly with AVS is lacking. This study aims to evaluate the diagnostic accuracy of CXCR4-PET/CT and to determine whether PET imaging can support treatment decision-making. Methods and analysis This prospective single-centre diagnostic test accuracy study will enrol adults with confirmed PA and blood pressure ≥140/90 mm Hg. All participants will undergo adrenal CT, CXCR4-PET/CT and AVS following standardised protocols. Diagnostic accuracy will be evaluated by receiver operating characteristic curve, using a hierarchical reference standard, with AVS as the primary clinical reference and postoperative histopathology (according to the International Histopathology Consensus for Unilateral Primary Aldosteronism). Eligible patients may receive superselective adrenal arterial embolisation (SAAE), adrenalectomy or medical therapy. Clinical and biochemical outcomes, including blood pressure, aldosterone-renin parameters and medication burden, will be assessed at 1, 3, 6 and 12 months. Safety will be monitored and graded using Common Terminology Criteria for Adverse Events (CTCAE) V.5.0 criteria. Multivariable analyses will explore predictors of unilateral disease and factors associated with PET–AVS discordance. Ethics and dissemination By integrating functional imaging, AVS, and treatment outcomes within a unified prospective framework, this study may provide comprehensive evaluations of CXCR4-PET/CT in PA to date. Findings may clarify its diagnostic utility, reduce dependence on AVS, and support precision treatment strategies in PA management. Trial registration number ChiCTR2600118245.