The value of 68Ga-Pentixafor PET/CT targeting CXCR4 in the diagnosis of ACTH-independent Cushing syndrome.

ACTH-independent Cushing syndrome (CS), a form of endogenous CS and an adrenal cause of hypertension, presents specific challenges in localizing cortisol-producing lesions. This study compared the diagnostic utility of 68Ga-Pentixafor PET/CT for lesion localization between ACTH-independent CS and non-functioning adrenal adenomas (NFAA). We retrospectively analyzed 73 subjects (52 with ACTH-independent CS; 21 with NFAA) undergoing 68Ga-Pentixafor PET/CT. Visual analysis demonstrated high diagnostic accuracy, with a sensitivity of 91.95%, a specificity of 95.24%, and a Youden index of 0.87. In semi-quantitative analysis, the lesion-to-adrenal ratio (LAR) showed superior performance compared to SUVmax and lesion-to-liver ratio (LLR). Using a diagnostic cutoff of SUVmax > 1.30, the sensitivity and specificity were 100% and 76.20%, respectively, supported by an AUC of 0.935 (P < 0.001) and a Youden index of 0.762. 68Ga-Pentixafor PET/CT effectively localizes functional adrenal lesions in ACTH-independent CS with high accuracy, supporting its role in guiding targeted management and surgical planning.