KCNJ5-Dependent 68Ga-Pentixafor PET/CT in Primary Aldosteronism Surgery

Abstract 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.