Functional nodules in primary aldosteronism: identification of CXCR4 expression with ${}^{68}$Ga-pentixafor PET/CT

We analyzed the diagnostic efficiency of ${}^{68}$Ga-pentixafor PET/CT for functional nodules in primary aldosteronism (PA). Furthermore, we compared the correlation of CXCR4 expression with aldosterone synthase (CYP11B2) expression and PET/CT uptake in these patients. We prospectively assessed 50 patients diagnosed with PA and 10 patients with non-functional adrenal adenoma (NFA). All patients underwent ${}^{68}$Ga-pentixafor PET/CT before adrenalectomy. Immunohistochemistry (IHC) was performed to detect the protein expression of CYP11B2 and the G-protein-coupled receptor CXCR4. CYP11B2 IHC revealed the presence of 43 functional nodules. Subsequently, 40/43 functional nodules could be detected on ${}^{68}$Ga-pentixafor PET/CT, while negative imaging findings were noted for 11/13 non-functional nodules (sensitivity, 93.0%; specificity, 84.6%). The optimum SUV${}_{max}$ cut-off for the identification of functional nodules was 8.95 (AUC 0.914 [0.828-1.000], p < 0.001). Regarding the size of functional nodules, diagnostic efficiency appeared to be much higher for nodules greater than 1 cm in size (sensitivity, up to 97.3%). Moreover, we examined the relationship between CXCR4 and CYP11B2 expression in 56 lesions. All 43 CYP11B2-positive nodules were CXCR4-positive, but one of the 13 CYP11B2-negative nodules (7.7%) showed false-positive staining for CXCR4. Moreover, the consistency between PET/CT uptake and CXCR4 staining results was 92.9% (52/56). At least 90% of functional nodules show positive uptake on ${}^{68}$Ga-pentixafor PET/CT, and the detection ability is much better for nodules with a diameter ≥ 1 cm. With its high sensitivity and specificity, ${}^{68}$Ga-pentixafor PET/CT can be considered a promising surgical decision-making tool for patients with PA. ${}^{68}$Ga-pentixafor PET/CT could be a useful tool for the identification of functional adrenal nodules in APAs and even IHAs. The diagnostic efficiency appears to be much higher for nodules ≥ 1 cm in size. There is high consistency between the results of 68Ga-pentixafor PET/CT imaging and CXCR4 immunohistochemistry.