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 (Ga-68-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 Ga-68-pentixafor PET/CT, and 11 with pituitary adenoma also underwent F-18-FDG PET/CT. The diagnosis accuracy of Ga-68-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 Ga-68-pentixafor in adrenal lesions but not in the pituitary fossa. The nonfunctioning pituitary or adrenal adenomas showed negative Ga-68-pentixafor signal. The one patient with metastatic ectopic ACTH syndrome had multiple Ga-68-pentixafor-avid lesions. Using the threshold of SUVmax >8.5 in the adrenal lesions, the sensitivity and specificity of Ga-68-pentixafor PET/CT to diagnose cortisol-producing adenoma were 100% and 84.9%. A cutoff SUVmax value of 3.0 on Ga-68-pentixafor PET/CT had 100% sensitivity and specificity for differentiating ACTH-PA. The corresponding hormone level was significantly correlated with uptake of Ga-68-pentixafor in pituitary adenoma and adrenal tissue but not with glucose metabolism. Conclusion We have characterized the performance of Ga-68-pentixafor in different subtypes of CS. Ga-68-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.