Diagnostic Performance of 68Ga DOTA-Pentixafor PET/CT in Benign Functional Adrenal Cortical Lesions

Objective: – This prospective study evaluated the diagnostic performance of 68Ga DOTA-Pentixafor PET/CT in characterizing the functional properties and lateralization of aldosterone-producing and cortisol-producing adrenal cortical lesions. The contribution of Pentixafor PET/CT to diagnosis and treatment planning was assessed in comparison with CT, MRI, and 18F-FDG PET/CT. Patients and Methods: – Twenty-five patients with suspected benign functional adrenal cortical masses were included. All patients underwent whole-body imaging at 1 hour and delayed abdominal imaging at 2 hours following intravenous administration of 18F-FDG and 68Ga DOTA-Pentixafor. Lesion SUVmax, LCRSUVmax, and LLRSUVmax values were analyzed and correlated with laboratory parameters, other imaging modalities, and postoperative clinical and pathologic outcomes. Results: – 68Ga DOTA-Pentixafor PET/CT demonstrated distinct focal uptake relative to the contralateral adrenal gland and liver parenchyma in 6/6 (100%) patients with suspected PA, 5/18 (27.7%) with suspected CS, and 1/1 (100%) with suspected EAS. Among patients with focal uptake who underwent surgery, all PA (5/5) and all CS (5/5) cases were confirmed as adrenocortical adenomas, resulting in no false-positive findings (PPV 100%). However, due to 2 false-negative CS cases, pentixafor PET/CT demonstrated an overall sensitivity of 83.3%, specificity of 100%, and accuracy of 85.7%. Thresholds of SUVmax >15.11, LCRSUVmax >1.74, and LLRSUVmax >4.36 yielded sensitivities of 33.3%, 41.7%, and 41.7%, respectively, while maintaining 100% specificity. Clinical and biochemical improvement was observed in 100% (5/5) of operated PA patients and 100% (5/5) of operated CS patients. Follow-up of nonoperated patients is ongoing. Conclusion: – 68Ga DOTA-Pentixafor PET/CT is a valuable diagnostic and potentially therapeutic tool for benign functional adrenal cortical disorders such as PA, CS, and EAS, with the potential to establish a new standard in minimally invasive patient management. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.