Clinical implications of ⁶⁸Ga-pentixafor PET/CT in surgically treated primary aldosteronism

CXCR4-targeted positron emission tomography/computed tomography has demonstrated potential utility in functional characterization and lateralization assessment of primary aldosteronism. However, clinical implications for postoperative outcomes after adrenalectomy and biologic correlations with adrenal histopathology remain incompletely defined in surgical cohorts.

We retrospectively analyzed data from 188 patients with primary aldosteronism who underwent CXCR4-targeted ⁶⁸Ga-pentixafor positron emission tomography/computed tomography before adrenalectomy. Quantitative positron emission tomography/computed tomography parameters reflecting positron emission tomography tracer uptake were measured, and their associations with postsurgical clinical and biochemical outcomes were analyzed according to Primary Aldosteronism Surgical Outcome score. Associations with histopathologic subtypes defined by the histopathology of primary aldosteronism consensus and CYP11B2 expression were analyzed as supportive biologic correlates.

After a median follow-up of at least 6 months, patients achieving complete clinical success exhibited smaller tumor volume but higher tracer uptake parameters, including maximum standardized uptake value, mean standardized uptake value, and lesion-to-background ratios (lesion-to-ipsilateral cortex ratio, lesion-to-contralateral cortex ratio, and lesion-to-liver ratio). Tumor volume remained independently associated with clinical success, whereas no positron emission tomography/computed tomography-derived parameter independently predicted complete biochemical success. Prognostic models incorporating positron emission tomography/computed tomography parameters demonstrated good discrimination for complete clinical and biochemical outcomes (area under the curve 0.853 and 0.861, respectively). In supportive analyses, classic HISTALDO subtypes showed higher maximum standardized uptake value and smaller tumor volume than nonclassic subtypes, with CYP11B2 immunoreactivity positively correlating with maximum standardized uptake value and CXCR4 expression.

In surgically treated primary aldosteronism, CXCR4-targeted ⁶⁸Ga-pentixafor positron emission tomography/computed tomography parameters were associated with postoperative clinical outcomes and may provide complementary information for postoperative risk stratification. Associations with histopathology of primary aldosteronism consensus subtypes likely reflect underlying biologic heterogeneity rather than independent diagnostic classification value.