⁶⁸Ga-Pentixafor PET/MRI for identifying corticotroph adenomas in Cushing disease: a pilot study

To assess whether C-X-C motif chemokine receptor 4-targeted ⁶⁸Ga-Pentixafor PET/MRI can localize corticotroph adenomas in patients with Cushing disease (CD), particularly when MRI is negative or inconclusive, and explore performance in newly diagnosed versus persistent/recurrent disease.

In this single-center pilot study, 10 patients with newly diagnosed or persistent/recurrent CD, confirmed by inferior petrosal sinus sampling (IPSS) and/or surgical pathology, underwent ⁶⁸Ga-Pentixafor PET/MRI. Clinical, biochemical, radiologic, surgical, and postoperative data were reviewed. ⁶⁸Ga-Pentixafor PET/MRI were classified as positive or negative using visual and quantitative assessment, including maximum standardized uptake values (SUVmax) and target-to-background (SUVmean of the blood pool in the cavernous sinus) ratio (TBR).

Participants had a mean age of 46.7 years; 9 were female. Five had newly diagnosed and 5 had persistent/recurrent CD. Two scans showed focal pituitary ⁶⁸Ga-Pentixafor uptake compared to background pituitary tissue. One was confirmed by an MRI-visible lesion, positive pathology, and postoperative remission. The second occurred with an inconclusive MRI, negative pathology, and persistent postoperative disease; however, IPSS centralized. Three patients with negative scans underwent surgery and achieved remission, indicating false-negative imaging. Among 5 patients with negative scans who did not undergo subsequent surgery, 4 had persistent/recurrent CD and 1 had newly diagnosed CD treated medically.

In this pilot cohort, ⁶⁸Ga-Pentixafor PET/MRI showed limited and variable performance for corticotroph adenoma localization. Although it may provide complementary information in selected patients with MRI-visible or equivocal lesions, further study is needed before it can be incorporated into diagnostic algorithms or considered an alternative to IPSS.