We aimed to investigate the diagnostic and prognostic value of ⁶⁸Ga-pentixafor PET/CT imaging in noncancer patients with suspected adrenal masses. Methods: Sixty-four patients who had benign adrenal masses on CT were retrospectively included in our study. All patients underwent ⁶⁸Ga-pentixafor PET/CT, and 56 of these patients subsequently underwent adrenalectomy. The subtypes of 81 adrenal tumors, including 14 nonfunctioning adrenal nodules, 4 cortisol-producing adenomas, 41 aldosterone-producing adenomas, 5 cases of suspected unilateral adrenal hyperplasia, 15 cases of idiopathic aldosterone hyperplasia, and 2 pheochromocytomas, were determined by histology or follow-up evaluations. The diagnostic efficiency of functional lateralization was calculated by visual analysis. Semiquantitative parameters of these lesions, including SUV_max, the ratio of lesional SUV_max to normal liver SUV_mean (LLR), and the ratio of lesional SUV_max to contralateral adrenal tissue SUV_mean (LCR), were also calculated. Dynamic analysis was also performed on 15 patients. In addition, clinical outcomes were assessed and compared in patients who underwent adrenalectomy. Results: The sensitivity and specificity of ⁶⁸Ga-pentixafor PET for functional lateralization in patients with adrenocortical lesions were 97.8% (45/46) and 87.5% (14/16), respectively. The 2 pheochromocytoma lesions had lower pentixafor uptake than the normal adrenal glands. Functioning (active) adrenocortical adenomas showed an elevated SUV_max of 16.3 ± 7.9, in comparison to 4.4 ± 1.7 in nonfunctioning (inactive) adenomas and 5.5 ± 2.7 in hyperplasia lesions (P < 0.0001). To identify active adrenocortical adenomas, a cutoff of 7.1 for SUV_max showed a sensitivity of 90.9% and a specificity of 85.3% (area under receiver-operating-characteristic curve, 0.96; P < 0.0001); a cutoff of 2.5 for LLR showed a sensitivity of 95.5% and a specificity of 88.2% (area under receiver-operating-characteristic curve, 0.97; P < 0.0001); and a cutoff of 2.4 for LCR showed a sensitivity of 88.6% and a specificity of 91.8% (area under receiver-operating-characteristic curve, 0.95; P < 0.0001). The graphical influx rate constant of active adrenocortical adenomas was significantly higher than that of inactive adenomas. Uptake values for ⁶⁸Ga-pentixafor were significantly higher in patients with preferable outcomes (cured/improved) (SUV_max, 15.5 ± 8.0; LLR, 6.5 ± 4.3; LCR, 6.2 ± 5.0) than in patients with nonpreferable outcomes (no improvement) (SUV_max, 4.2 ± 0.5; LLR, 1.3 ± 0.2; LCR, 1.5 ± 0.6; all P < 0.0001). Conclusion:⁶⁸Ga-pentixafor PET/CT imaging exhibits great potential for noninvasive functional lateralization and characterization in patients with adrenocortical masses.

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