Diagnostic accuracy of CXCR4-targeted PET/CT in primary aldosteronism: a systematic review and meta-analysis of 29 studies

Background CXCR4-targeted PET/CT with radiotracers such as ⁶⁸Ga-pentixafor is gaining attention due to high CXCR4 receptor expression in Aldosterone-producing adenoma (APA). In this review, we aim to provide the most comprehensive and up-to-date assessment of the diagnostic accuracy and clinical utility of CXCR4-targeted PET/CT in APA patients. Methods Following the PRISMA guidelines, we searched three databases for studies that utilized CXCR4-targeted PET/CT in patients with APA. The primary outcomes were sensitivity, specificity, and accuracy using both univariate and bivariate pooling methods for diagnostic test accuracy meta-analysis. Results A total of 29 studies were included. A bivariate random-effects meta-analysis was performed to evaluate the diagnostic accuracy of CXCR4-targeted PET/CT for lateralizing primary aldosteronism (PA). The sensitivity was 0.807 (95% CI [0.759–0.848]), and the specificity was 0.76 (95% CI [0.665–0.835]). The HSROC AUC was 0.85, and the normalized partial AUC (for restricted false positive rates) was 0.817. Between-study heterogeneity, evaluated using the methods of Zhou and Dendukuri, was low (I² = 9.8%). The univariate random-effects meta-analysis showed that sensitivity was 0.83 (95% CI: 0.776–0.874), specificity was 0.821 (95% CI: 0.700–0.901), and overall accuracy was 0.823 (95% CI: 0.774–0.862). The PPV was high at 0.918 (95% CI: 0.860–0.953), while the NPV was low at 0.671 (95% CI: 0.564–0.763), demonstrating moderate to substantial heterogeneity across these estimates (I² = 43.8%-67.2%). Conclusion CXCR4-targeted PET/CT shows potential as an adjunct for selected patients, but current evidence does not support replacing AVS or PET-guided surgery outside established protocols.