⁶⁸GA-Pentixafor PET/CT: a non-invasive molecular alternative to adrenal venous sampling in primary aldosteronism

Primary aldosteronism (PA) is the most common cause of secondary hypertension, where accurate subtype differentiation between unilateral aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH) determines therapeutic strategy. Adrenal venous sampling (AVS) remains the reference standard but is invasive, technically demanding, and not widely available. Recent advances in molecular imaging have introduced CXCR4-targeted positron emission tomography using ⁶⁸Ga-Pentixafor as a promising non-invasive tool for functional characterization and lateralization of aldosterone-producing lesions. CXCR4 is highly expressed in the zona glomerulosa and in aldosterone-producing adenomas, and it closely correlates with CYP11B2 (aldosterone synthase) expression. Across multiple clinical studies, ⁶⁸Ga-Pentixafor PET/CT has demonstrated high diagnostic accuracy, with reported sensitivities ranging from 74% to 98% and specificities from 84% to 100%, showing substantial concordance with AVS findings. In addition, PET-guided adrenalectomy yields biochemical and clinical outcomes comparable to AVS-guided management while avoiding procedural risks. By targeting CXCR4 expression, ⁶⁸Ga-Pentixafor PET/CT offers reliable lateralization with good agreement to AVS and strong clinicopathological correlation. Ongoing studies will further clarify its diagnostic role and integration into routine evaluation of primary aldosteronism.