Background Gallium 68 (⁶⁸Ga) pentixafor has emerged as a potential C-X-C chemokine receptor type 4 (CXCR4)-targeted radiotracer for neuroendocrine tumor, yet its application in Cushing disease remains uncertain. Purpose To assess the diagnostic accuracy and value of ⁶⁸Ga-pentixafor PET/MRI in localizing adrenocorticotropic hormone (ACTH)-secreting pituitary tumors in Cushing disease. Materials and Methods A prospective single-center study was conducted from March 2023 to February 2024 in participants with Cushing disease scheduled for surgical pituitary tumor resection. All participants underwent preoperative ⁶⁸Ga-pentixafor PET/MRI and contrast-enhanced MRI. Two radiologists and nuclear medicine physicians analyzed images. Surgical and histologic findings served as the reference standard. Diagnostic performance was compared using the McNemar test. The Wilcoxon signed rank test was used to compare the maximum standardized uptake value (SUV_max) between tumor and normal pituitary. Correlations between SUV_max and histopathologic or hormone characteristics were analyzed using the Spearman coefficient and logistic regression tests. Results A total of 43 participants (median age, 37 years [IQR, 31-49 years]; 35 female) were included, with 44 pituitary lesions identified after investigational imaging scans, 41 of which were confirmed as ACTH secreting. Sensitivity and diagnostic accuracy of ⁶⁸Ga-pentixafor PET/MRI were 92.7% (38 of 41 lesions; 95% CI: 80.6, 97.5) and 88.6% (39 of 44 lesions; 95% CI: 76.0, 95.0), respectively, which were higher compared with that of contrast-enhanced MRI (78.0% [32 of 41 lesions; 95% CI: 63.3, 88.0] and 77.3% [34 of 44 lesions; 95% CI: 63.0, 87.2], respectively). Both techniques combined improved sensitivity to 100% (41 of 41 lesions; 95% CI: 91.4, 100.0) and accuracy to 95.5% (42 of 44 lesions; 95% CI: 84.9, 99.2) (P = .01). ACTH-secreting pituitary tumors exhibited a higher SUV_max than normal pituitary (3.9 vs 1.3, P < .001). The SUV_max exhibited a positive correlation with CXCR4 H-score (R = 0.5 [95% CI: 0.2, 0.7], P < .001) and ACTH levels (R = 0.4 [95% CI: 0.1, 0.6], P = .01). Conclusion ⁶⁸Ga-pentixafor PET/MRI demonstrated high sensitivity in localizing ACTH-secreting pituitary tumors. ⁶⁸Ga-pentixafor uptake was associated with CXCR4 expression and ACTH level. © RSNA, 2024 Supplemental material is available for this article.

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