KCNJ5-dependent 68Ga-pentixafor positron emission tomography/computed tomography in primary aldosteronism surgery

PURPOSE: To evaluate 68Ga-pentixafor PET/CT in the surgical management of primary aldosteronism (PA), with emphasis on its relationship with adrenal venous sampling (AVS), KCNJ5 mutation status, tracer uptake, and postoperative outcomes. PATIENTS AND METHODS: This retrospective single-center cohort screened 929 consecutive patients with suspected PA from November 2021 to February 2025. The final cohort included 162 patients who underwent unilateral adrenalectomy and 6-month follow-up; 83 also underwent AVS. Patients treated before September 2024 followed an AVS-guided pathway, and those treated thereafter followed a PET/CT-guided pathway. Outcomes were assessed by PASO criteria. Firth logistic regression, overlap weighting, paired PET/CT-versus-AVS analysis, and genotype-stratified analyses were performed. RESULTS: Clinical and biochemical complete success did not differ significantly between the PET-guided and AVS-guided groups. Among patients with both tests, unilateral PET/CT showed high positive predictive value versus AVS (56/57, 98.2%), but 26 of 82 AVS-confirmed unilateral PA cases had negative or bilateral PET findings. All KCNJ5-mutated patients in the PET-status cohort were PET-positive, whereas 22 of 52 KCNJ5-nonmutated patients were PET-negative. KCNJ5 mutation and CT lesion size were independently associated with PET positivity. SUVmax LI was associated with biochemical complete success, including within KCNJ5-nonmutated patients. CONCLUSIONS: 68Ga-pentixafor PET/CT provides strong rule-in information when uptake is clearly unilateral. Negative or bilateral PET/CT, especially in small or KCNJ5-nonmutated lesions, should be interpreted cautiously and should not preclude AVS-based evaluation.