SUN-017 - Efficacy of 68Ga-Pentixafor PET/MRI for Identifying Corticotroph Adenomas: A Pilot Study

Background:
In Cushing’s disease (CD), 85% of the culprit lesions are microadenomas and 40% are too small to be visualized on contrast-enhanced MRI. Many patients with ACTH-dependent Cushing’s require inferior petrosal sinus sampling (IPSS) to differentiate pituitary from ectopic disease, but IPSS is unable to locate the adenoma within the sella. C-X-C motif chemokine receptor 4 (CXCR4) may be overexpressed in functional pituitary adenomas, and limited data suggest that CXCR4 molecular imaging with 68Ga-Pentixafor PET/MRI may be helpful for identifying small corticotroph adenomas.

Purpose:
To assess the ability of CXCR4-targeted PET/MRI to 1) identify corticotroph adenomas not seen on contrast-enhanced MRI; 2) indicate the presence of a functional corticotroph microadenoma visualized on MRI that would otherwise still require IPSS for localization and 3) inform future surgical vs non-surgical management.

Methods:
In a single-center pilot study, 10 patients with new or persistent/recurrent CD, confirmed by IPSS and/or positive surgical pathology, underwent 68Ga-Pentixafor PET/MRI imaging. Chart review provided biochemical, radiologic, and surgical data. Pentixafor results were assessed as either positive or negative using visual and quantitative methods, including standardized uptake value (SUV) and the tumor-to-background ratio. MRI results were considered positive, negative, or inconclusive using gadolinium-enhanced T1-weighted imaging.

Results:
Of the 10 participants (mean age 46.7; 9 female), 5 had new and 5 had persistent/recurrent disease. 5 patients underwent transsphenoidal surgery (TSS) following Pentixafor imaging. Two participants had a positive Pentixafor scan with presence of a focal area of [^68Ga]-Pentixafor uptake within the pituitary. One patient represented a true positive result, with an MRI-identified lesion, positive pathology, and post-operative remission. The other patient had an inconclusive MRI, negative pathology, and persistent disease post-operatively, but given a centralizing IPSS, this may also represent a true positive in whom tumor was not surgically identified. The 3 participants with negative Pentixafor scans who underwent subsequent TSS had new CD and achieved post-operative remission (false negatives results). Of the 5 patients with negative Pentixafor scans who did not undergo subsequent TSS, 4 had persistent/recurrent CD on pharmacotherapy, and 1 had new CD who declined TSS in favor of medical therapy.

Conclusion:
Data from this pilot study suggest that 68Ga-Pentixafor PET/MRI may help localize corticotroph adenomas in the setting of primary disease that is visible on MRI, potentially allowing these patients to avoid IPSS prior to TSS. In our cohort, 68Ga-Pentixafor PET/MRI did not identify adenomas in the setting of MRI-negative disease, particularly in the cases of persistent/recurrent disease.

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