Pooled diagnostic accuracy of 68Ga-pentixafor PET/CT for aldosterone-producing lesions in primary aldosteronism

BACKGROUND Primary aldosteronism is a leading cause of secondary hypertension and is associated with increased cardiovascular risk. Accurate localization of aldosterone-producing lesions is essential to guide curative treatment. Although adrenal venous sampling (AVS) remains the gold standard for subtyping, it is invasive and not widely available. Recent advances in molecular imaging, including 68Ga-Pentixafor PET/CT targeting CXCR4, have shown potential for non-invasive localization of functional adrenal lesions. PURPOSE To assess the pooled diagnostic accuracy of 68Ga-Pentixafor PET/CT for detecting aldosterone-producing lesions. METHODS A systematic review and meta-analysis were conducted following PRISMA-DTA guidelines. Databases including PubMed, Embase, Scopus, Web of Science, and CENTRAL were searched through January 2025. Eligible studies included adult patients with primary aldosteronism who underwent 68Ga-Pentixafor PET/CT, with reference standards including AVS, histopathology, or immunohistochemistry. Diagnostic accuracy outcomes were pooled using a bivariate random-effects model. RESULTS Eight studies comprising 564 patients were included. Agreement between reviewers during full-text assessment was almost perfect (Cohen's κ = 0.93). Pooled sensitivity was 83% (95% CI: 75-89), specificity 94% (95% CI: 83-98), AUC 0.91 (95% CI: 0.88-0.93), LR+ 14.6 (95% CI: 5.3-40.2), and LR- 0.18 (95% CI: 0.12-0.27). Diagnostic performance remained stable across subgroups, with no significant variation according to tracer dose, SUVmax, acquisition time, study design, or CXCR4/CYP11B2 expression. No evidence of publication bias was detected (Deeks' test, p = 0.93). CONCLUSIONS 68Ga-Pentixafor PET/CT demonstrates high diagnostic accuracy for identifying aldosterone-producing lesions and may serve as a reliable, non-invasive alternative to AVS in selected patients.