Abstract Background ⁶⁸Ga-Pentixafor PET/CT (Pent-PET) targets CXCR4 expression and represents a non-invasive alternative to adrenal venous sampling. However, validation of imaging findings against CXCR4 immunohistochemistry in resected adrenal tissue is limited. This study evaluates the diagnostic performance of Pent-PET for aldosterone producing adenomas (APA) localization using immunohistochemical CXCR4 expression as reference. Method A prospective cohort of 52 patients with primary aldosteronism underwent Pent-PET (9/2022 – 12/2025). The diagnosis of hyperaldosteronism was confirmed by biochemical testing. PET/CT was considered positive if focal tracer uptake was visible on imaging; a definitive SUVmax cut-off value was not available. Twenty-five patients proceeded to adrenalectomy, followed by histopathological evaluation including CXCR4 immunohistochemistry. Pent-PET-based lateralisation was compared with surgical pathology, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results Pent-PET demonstrated bilateral tracer uptake in 2 patients, unilateral uptake in 15 patients, and yielded indeterminate findings in 8 cases. Surgical procedures included unilateral adrenalectomy (n=17), partial adrenalectomy (n=5), and bilateral adrenalectomy (n=3). Histopathological analysis revealed 17 adenomas (including 3 bilateral resection) and 8 hyperplasias. CXCR4 immunohistochemistry was positive in 12 specimens. Clinical follow-up showed biochemical and/or clinical improvement in 17 patients (7 cure, 8 improvement of hypertension, 3 isolated biochemical improvement). The diagnostic accuracy of Pent-PET for lateralising APAs: sensitivity 52%, specificity 62%, PPV 75%, and NPV 62%. Conclusion ⁶⁸Ga-Pentixafor PET/CT shows moderate diagnostic accuracy for APA localisation when validated against CXCR4 immunohistochemistry. Its limited sensitivity supports its use as a complementary tool rather than a replacement for adrenal venous sampling.
Kounnamas et al. (2026) studied this question.