Real world experience with [68Ga]PentixaFor PET/CT in Primary Aldosteronism using newly developed harmonized diagnostic criteria

Background Positron emission tomography (PET) of the adrenal glands emerged as a non-invasive alternative to adrenal vein sampling (AVS) for treatment selection in primary aldosteronism (PA). The C-X-C-chemokine-receptor type 4 targeting tracer [ 68 Ga]PentixaFor showed potential in visualizing aldosterone-producing adenomas. However, standardized diagnostic criteria and experience in European cohorts remain scarce. Here, we report harmonized PET/CT interpretation criteria, assess their impact on diagnostic agreement, and present a large European tertiary center’s experience with [ 68 Ga]PentixaFor PET/CT in PA. Methods Between 11/2023 and 01/2025, 35 consecutive PA patients underwent [ 68 Ga]PentixaFor PET/CT; 22 also underwent AVS. PET/CT scans were interpreted in three independent, blinded reads, in which inter-reader agreement was assessed: (i) the routine clinical read by the local team, (ii) an independent review by external molecular imaging experts, (iii) a local re-evaluation using harmonized criteria adapted from experience with [ 11 C]Metomidate PET. Surgical outcomes were analyzed according to Primary Aldosteronism Surgery Outcome (PASO) criteria. Results Agreement between local and external readings was 80% (28/35), increasing to 94% (33/35) after applying harmonized PET/CT criteria. Based on local readings, 18/35 scans (51%) were interpreted as unilateral. In contrast, both the external review and the local team’s re-evaluation classified 11/35 (31%) as high probability, and 10/35 (29%) as intermediate probability of unilateral PA. According to local AVS criteria, 10/14 interpretable AVS indicated unilateral disease, with 8/10 concordant on PET. Combining successfully and partially cannulated AVS with PET findings, high confidence to diagnose unilateral disease increased to 12/22 (55%) patients. Twelve patients underwent adrenalectomy with PASO outcomes assessed ≥ 6 months after surgery, identified by AVS, PET or both (n=3, n=8 and n=1, respectively). Complete biochemical remission occurred in 2/3 operated patients based on AVS, 6/8 operated patients informed by PET, and 1/1 guided by both. Conclusion [ 68 Ga]PentixaFor PET continues to show promise for non-invasive PA subtyping. Harmonized interpretation criteria substantially improved inter-reader agreement. When combined with (partial) AVS, PET increases diagnostic confidence and may expand access to definitive treatment. Further studies are warranted to validate the proposed PET interpretation criteria and better define the subset of patients in whom [ 68 Ga]PentixaFor PET/CT alone might suffice for PA subtyping.