⁶⁸Ga-Pentixafor Positron Emission Tomography/Computed Tomography in Primary Aldosteronism: Preliminary Analysis on Contrast-Enhanced Computed Tomography Concordance and Positron Emission Tomography/Computed Tomography Avidity Patterns

Abstract

⁶⁸Ga-Pentixafor positron emission tomography/computed tomography has shown potential in primary aldosteronism subtyping, but analysis of its diagnostic accuracy based on contrast-enhanced computed tomography concordance and positron emission tomography/computed tomography avidity patterns is lacking. The objective of this study was to evaluate the diagnostic accuracy of ⁶⁸Ga-Pentixafor positron emission tomography/computed tomography for subtyping primary aldosteronism and to assess its performance based on concordance with contrast-enhanced computed tomography and positron emission tomography/computed tomography avidity patterns. Clinical, biochemical, radiological, functional imaging, treatment, histopathological, and follow-up details of 30 patients with primary aldosteronism who underwent positron emission tomography/computed tomography over 2 years at a tertiary center in India were retrospectively analyzed. Diagnostic accuracy of positron emission tomography/computed tomography for primary aldosteronism subtyping was evaluated in the whole cohort and in subgroups based on contrast-enhanced computed tomography–positron emission tomography/computed tomography concordance and positron emission tomography/computed tomography avidity patterns. Out of the 30 patients, final subtype classification was achieved in 15 (9 unilateral and 6 bilateral) based on surgical outcomes and/or adrenal venous sampling. Positron emission tomography/computed tomography correctly subtyped 14/15 (93.3%) patients. Contrast-enhanced computed tomography and positron emission tomography/computed tomography concordance was seen in 10 patients, and positron emission tomography/computed tomography accuracy was 100% (10/10) in this subgroup. Contrast-enhanced computed tomography and positron emission tomography/computed tomography discordance (contrast-enhanced computed tomography bilateral and positron emission tomography/computed tomography unilateral) was seen in five patients, and positron emission tomography/computed tomography accuracy in this subgroup was 80% (4/5). Positron emission tomography/computed tomography avidity patterns in the 15 patients having final subtype classification were unilateral avid (n=10), bilateral avid (n=2), and bilateral nonavid (n=3). Diagnostic accuracy of positron emission tomography/computed tomography was 90% (9/10) in patients with unilateral avidity, and 100% in those with bilateral avidity or nonavidity. Preliminary analysis suggests that positron emission tomography/computed tomography demonstrates higher accuracy in certain subgroups, potentially guiding the triage for adrenal venous sampling.

Keywords

⁶⁸Ga-Pentixafor - PET/CT - primary aldosteronism - subtyping - CT concordance

• References

• 1 Mullen N, Curneen J, Donlon PT. et al. Treating primary aldosteronism-induced hypertension: novel approaches and future outlooks. Endocr Rev 2024; 45: 125-170
• 2 Mulatero P, Monticone S, Bertello C. et al. Long-term cardio- and cerebrovascular events in patients with primary aldosteronism. J Clin Endocrinol Metab 2013; 98: 4826-4833
• 3 Vaidya A, Hundemer GL, Nanba K. et al. Primary aldosteronism: state-of-the-art review. Am J Hypertens 2022; 35: 967-988
• 4 Parksook WW, Yozamp N, Hundemer GL. et al. Morphologically normal-appearing adrenal glands as a prevalent source of aldosterone production in primary aldosteronism. Am J Hypertens 2022; 35: 561-571
• 5 Sam D, Kline GA, So B. et al. Discordance between imaging and adrenal vein sampling in primary aldosteronism irrespective of interpretation criteria. J Clin Endocrinol Metab 2019; 104: 1900-1906
• 6 Funder JW, Carey RM, Mantero F. et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016; 101: 1889-1916
• 7 Wu X, Senanayake R, Goodchild E. et al. [11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial. Nat Med 2023; 29: 190-202
• 8 Heinze B, Fuss CT, Mulatero P. et al. Targeting CXCR4 (CXC chemokine receptor type 4) for molecular imaging of aldosterone-producing adenoma. Hypertension 2018; 71: 317-325
• 9 Yin X, Ai K, Luo J. et al. A comparison of the performance of ⁶⁸Ga-Pentixafor PET/CT versus adrenal vein sampling for subtype diagnosis in primary aldosteronism. Front Endocrinol 2024; 15: 1291775
• 10 Zheng Y, Long T, Peng N. et al. The value of targeting CXCR4 with ⁶⁸Ga-Pentixafor PET/CT for subtyping primary aldosteronism. J Clin Endocrinol Metab 2023; 109: 171-182
• 11 Zhang X, Song Y, Jing Y. et al. Comparison of different diagnostic criteria of ⁶⁸Ga-Pentixafor PET/CT for the classification of primary aldosteronism. J Clin Endocrinol Metab 2025; 110: e2583-e2590
• 12 Yi T, Lu D, Cui Y. et al. ⁶⁸Ga-pentixafor PET/CT is a supplementary method for primary aldosteronism subtyping compared with adrenal vein sampling. Mol Imaging Biol 2025; 27: 142-150
• 13 Lu N, Chen L, Yu F. et al. Evaluating the value of chemokine receptor type 4–targeted PET imaging in diagnosing primary aldosteronism lateralization: a comparison with adrenal venous sampling. Surgery 2025; 181: 109156
• 14 Peng Y, Chen F, Yao R. et al. The value of targeted CXCR4 18F-AlF-NOTA-pentixafor PET/CT for subtyping primary aldosteronism. Front Endocrinol 2025; 16: 1533295
• 15 Goroshi M, Jadhav SS, Sarathi V. et al. Radiological differentiation of phaeochromocytoma from other malignant adrenal masses: importance of wash-in characteristics on multiphase CECT. Endocr Connect 2019; 8: 898-905
• 16 Dekkers T, Prejbisz A, Kool LJS. et al. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial. Lancet Diabetes Endocrinol 2016; 4: 739-746
• 17 Zuo R, Liu S, Ren X. et al. Typing diagnostic value of ⁶⁸Ga-pentixafor PET/CT for patients with primary aldosteronism and unilateral nodules. Endocrine 2024; 87: 314-324
• 18 Rathod K, Memon SS, Mahajan P. et al. Adrenal venous sampling in primary aldosteronism: single-centre experience from Western India. Indian J Endocrinol Metab 2023; 27: 80-86
• 19 Menon SR, Sahu S, Mitra A. et al. On the automated radiosynthesis of pharmaceutical grade [⁶⁸Ga]Ga-Pentixafor, its pre-clinical evaluation, clinical application and radiation dosimetry aspects. Sci Rep 2025; 15: 6476
• 20 Hu J, Xu T, Shen H. et al. Accuracy of Gallium-68 Pentixafor positron emission tomography–computed tomography for subtyping diagnosis of primary aldosteronism. JAMA Netw Open 2023; 6: e2255609
• 21 Williams TA, Lenders JWM, Mulatero P. et al. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol 2017; 5: 689-699
• 22 Turcu AF, Yang J, Vaidya A.. Primary aldosteronism — a multidimensional syndrome. Nat Rev Endocrinol 2022; 18: 665-682
• 23 DePietro DM, Fraker DL, Wachtel H. et al. “Double-Down” adrenal vein sampling results in patients with apparent bilateral aldosterone suppression: utility of repeat sampling including super-selective sampling. J Vasc Interv Radiol 2021; 32: 656-665
• 24 Tan SYT, Ng KS, Tan C. et al. Bilateral aldosterone suppression in patients with right unilateral primary aldosteronism and review of the literature. J Endocr Soc 2020; 4bvaa033
• 25 Zheng G, Ding J, Gao Y. et al. ⁶⁸Ga-pentixafor PET/CT in guiding surgical management of primary aldosteronism. J Clin Transl Endocrinol 2025; 39: 100384