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Usefulness of 68Ga-Pentixafor PET/CT on Diagnosis and Management of Cushing Syndrome

Purpose This pilot study investigated the performance of C-X-C motif chemokine receptor 4 (CXCR4) molecular imaging (68Ga-pentixafor PET/CT) in Cushing syndrome (CS) and the correlation between CXCR4 signaling interactions and glucose metabolism in adrenocorticotropin-cortisol pathway. Methods We retrospectively evaluated 31 patients (16 patients with CS and 15 patients with nonfunctioning pituitary or adrenal adenomas). All patients underwent 68Ga-pentixafor PET/CT, and 11 with pituitary adenoma also underwent 18F-FDG PET/CT. The diagnosis accuracy of 68Ga-pentixafor PET/CT was calculated. The correlation between radiouptake along the pituitary-adrenal axis and hormone levels was calculated. Results Patients with Cushing disease characterized a focal uptake in adrenocorticotropic hormone–producing pituitary adenoma (ACTH-PA). In ACTH-independent CS, there was increased uptake of 68Ga-pentixafor in adrenal lesions but not in the pituitary fossa. The nonfunctioning pituitary or adrenal adenomas showed negative 68Ga-pentixafor signal. The one patient with metastatic ectopic ACTH syndrome had multiple 68Ga-pentixafor–avid lesions. Using the threshold of SUVmax >8.5 in the adrenal lesions, the sensitivity and specificity of 68Ga-pentixafor PET/CT to diagnose cortisol-producing adenoma were 100% and 84.9%. A cutoff SUVmax value of 3.0 on 68Ga-pentixafor PET/CT had 100% sensitivity and specificity for differentiating ACTH-PA. The corresponding hormone level was significantly correlated with uptake of 68Ga-pentixafor in pituitary adenoma and adrenal tissue but not with glucose metabolism. Conclusion We have characterized the performance of 68Ga-pentixafor in different subtypes of CS. 68Ga-pentixafor PET/CT is promising in the differential diagnosis of both ACTH-independent and ACTH-dependent CS. Activated CXCR4 molecular signaling along the pituitary-adrenal axis was found in patients with Cushing disease.