ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Adrenal Endocrinology
Real world experience with [68Ga]PentixaFor PET/CT in Primary Aldosteronism using newly developed harmonized diagnostic criteria
Linus Hesse 1,2,3
Anna Herden 4
James MacFarlane 2
Daniel Gillett 2
Tina Kienitz 5
Sophie Howarth 2
Loreen Richter 1
Dominik Soll 1
Dominik Spira 1
Frederike Butz 6
Martina Mogl 7
Federico Collettini 8
Christian Strasburger 1,3
Lukas Maurer 1,3
Knut Mai 1,3,9
Mark Gurnell 2
Christian Furth 4
Linus Haberbosch 1,2,3
1. Department of Endocrinology and Metabolism; European Reference Network on Rare Endocrine Diseases (ENDO-ERN), 10117, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
2. Institute of Metabolic Science, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Hills Road, CB2 0QQ, Cambridge Endocrine Molecular Imaging Group, Cambridge, United Kingdom
3. Pituitary Tumor Center of Excellence at Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
4. Department of Nuclear Medicine, 13353, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
5. Endocrinology in Charlottenburg, 10627, Berlin, Germany
6. Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
7. Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117, Berlin, Germany
8. Department of Radiology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
9. Department of Human Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
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Abstract
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 [68Ga]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 [68Ga]PentixaFor PET/CT in PA. Methods Between 11/2023 and 01/2025, 35 consecutive PA patients underwent [68Ga]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 [11C]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 [68Ga]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 [68Ga]PentixaFor PET/CT alone might suffice for PA subtyping.
Summary
Keywords
[68Ga]pentixafor, adrenal molecularimaging, Adrenal vein sampling, positron emission tomography, primary aldosteronism
Received
13 January 2026
Accepted
17 February 2026
Copyright
© 2026 Hesse, Herden, MacFarlane, Gillett, Kienitz, Howarth, Richter, Soll, Spira, Butz, Mogl, Collettini, Strasburger, Maurer, Mai, Gurnell, Furth and Haberbosch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Linus Haberbosch
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