A Novel Non-Invasive Diagnostic Tool for Determining the Subtype of Primary Aldosteronism Using 68Ga Pentixafor PET/CT

Abstract Primary aldosteronism (PA) may present as either unilateral or bilateral disease. Differentiating unilateral forms—unilateral aldosterone– producing adenoma (APA) and unilateral adrenal hyperplasia—from bilateral forms—bilateral APA, bilateral adrenal hyperplasia (BAH)—is critical, as the management strategies differ. Currently, PA subtyping is performed using adrenal vein sampling (AVS) and computed tomography (CT). However, AVS is invasive and technically demanding, and CT has limited accuracy. CXCR4 (CXC chemokine receptor type 4) expression is higher in APAs than in normal adrenal tissue and non-functional tumors. Pentixafor, a CXCR4-specific ligand labelled with 68Ga, has shown potential for PA subtyping. This prospective observational study included 13 patients with confirmed PA who underwent 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT) and 13 individuals without PA as controls. Both visual and semi-quantitative analyses were used to classify patients with PA into unilateral or bilateral subtypes. Among the 13 patients with PA, 10 were diagnosed with unilateral primary aldosteronism (UPA) and three with bilateral primary aldosteronism (BPA) based on 68Ga-pentixafor PET/CT. The mean standardized uptake value (SUV)max, SUVratio, and adrenal/liver ratios were significantly higher in patients with UPA than in those with BPA and controls. The 10 patients with UPA underwent adrenalectomy, with histopathological and immunohistochemical analysis confirming the diagnosis. All 10 patients achieved complete biochemical remission post-surgery. The three patients with BPA were started on medical therapy and also achieved biochemical remission. 68Ga-Pentixafor PET/CT is a promising non-invasive imaging modality for PA subtyping and may serve as an alternative to AVS in cases where AVS is inconclusive, non-diagnostic, or contraindicated.