Diagnostic Accuracy and Value of CXCR4-targeted PET/MRI Using 68Ga-Pentixafor for Tumor Localization in Cushing Disease

Yue Wu; Yanfei Wu; Boyuan Yao; Shuhua Ren; Shiman Wu; Wenting Rui; Min He; Shuo Zhang; Yifei Yu; Hongying Ye; Zhaoyun Zhang; Zhen Ye; Rui Han; Nidan Qiao; Yichao Zhang; Xuejie Yu; Zengyi Ma; Yongfei Wang; Yao Zhao; Yihui Guan; Fang Xie; Qilin Zhang; Zhenwei Yao

doi:10.1148/radiol.233469

Diagnostic Accuracy and Value of CXCR4-targeted PET/MRI Using ⁶⁸Ga-Pentixafor for Tumor Localization in Cushing Disease

Radiology. 2024 Dec;313(3):e233469. doi: 10.1148/radiol.233469.

Authors

Yue Wu^#¹, Yanfei Wu^#¹, Boyuan Yao¹, Shuhua Ren¹, Shiman Wu¹, Wenting Rui¹, Min He¹, Shuo Zhang¹, Yifei Yu¹, Hongying Ye¹, Zhaoyun Zhang¹, Zhen Ye¹, Rui Han¹, Nidan Qiao¹, Yichao Zhang¹, Xuejie Yu¹, Zengyi Ma¹, Yongfei Wang¹, Yao Zhao¹, Yihui Guan¹, Fang Xie¹, Qilin Zhang^#¹, Zhenwei Yao^#¹

Affiliation

¹ From the Department of Radiology (Yue Wu, S.W., W.R., Z. Yao), Department of Neurosurgery, Shanghai Pituitary Tumor Center (B.Y., Z. Ye, R.H., N.Q., Y. Zhang, X.Y., Z.M., Y. Wang, Y. Zhao, Q.Z.), Department of Nuclear Medicine and PET Center (Yanfei Wu, S.R., Y.G., F.X.), and Department of Endocrinology (M.H., S.Z., Y.Y., H.Y., Z.Z.), Huashan Hospital, Fudan University, 12 Wulumuqi Road, Shanghai 200040, China; Neurosurgical Institute of Fudan University, Shanghai, China (B.Y., Z. Ye, R.H., N.Q., Y. Zhang, X.Y., Z.M., Y. Wang, Y. Zhao, Q.Z.); Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China (B.Y., Z. Ye, R.H., N.Q., Y. Zhang, X.Y., Z.M., Y. Wang, Y. Zhao, Q.Z.); Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China (B.Y., Z. Ye, R.H., N.Q., Y. Zhang, X.Y., Z.M., Y. Wang, Y. Zhao, Q.Z.); and Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Neuroendocrine Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, Mass (Q.Z.).

^# Contributed equally.

PMID: 39688484
DOI: 10.1148/radiol.233469

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Coordination Complexes / pharmacokinetics
Female
Gallium Radioisotopes
Humans
Magnetic Resonance Imaging* / methods
Male
Middle Aged
Multimodal Imaging / methods
Peptides, Cyclic* / pharmacokinetics
Pituitary ACTH Hypersecretion* / diagnostic imaging
Positron-Emission Tomography* / methods
Prospective Studies
Radiopharmaceuticals / pharmacokinetics
Receptors, CXCR4* / metabolism
Reproducibility of Results
Sensitivity and Specificity

Substances

68Ga-pentixafor
Receptors, CXCR4
Peptides, Cyclic
CXCR4 protein, human
Coordination Complexes
Gallium Radioisotopes
Radiopharmaceuticals