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Imaging CXCR4 expression in patients with suspected primary hyperaldosteronism

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

It is challenging to differentiate unilateral aldosterone-producing adenoma (APA) from bilateral idiopathic adrenal hyperplasia (IAH) and nonfunctional adrenal adenoma (NFA) in primary aldosteronism (PA). In a first primarily ex vivo study detection, CXC chemokine receptor type 4 (CXCR4) expression has been shown to be a valuable tool for the detection of APA. In this study, we aimed to clinically evaluate CXCR4 imaging with 68Ga-pentixafor PET/CT for detecting APA.

Methods

We prospectively recruited 36 patients with clinical suspicion of PA. All patients underwent 68Ga-pentixafor PET/CT. Positive lesions were defined based on higher tracer uptake in adrenal nodular(s) shown on CT than the normal adrenal. These lesions were referred for adrenalectomy subsequently. All patients received clinical follow-up. Semi-quantitative analysis using maximum standardized uptake value (SUVmax), lesion-to-liver ratio (LLR), and lesion-to-contralateral ratio (LCR) has also been performed. PET/CT results were correlated with clinical presentation and follow-up.

Results

Thirty-nine adrenal lesions in 36 patients were found; 25 APA, 4 IAH, and 10 NFA according to histopathology and clinical assessment. Sensitivity, specificity, and accuracy of 68Ga-pentixafor PET/CT in distinguishing APA by visualization were 100%, 78.6%, and 92.3% respectively. The SUVmax of APA (21.34 ± 9.41, n = 25) was significantly higher than that of non-APA lesions (6.29 ± 2.10, n = 14, P < 0.0001). An optimal threshold of SUVmax = 11.18 was determined for predicting APA with a sensitivity of 88.0%, specificity of 100%, and an accuracy of 92.3%. A cutoff value for LCR of 2.12 yielded a sensitivity of 100% and a specificity of 92.9%, whereas a cutoff value for LLR of 2.36 reached at both 100% of sensitivity and specificity. All patients with (removed) positive lesions benefited from surgery.

Conclusion

68Ga-Pentixafor PET/CT may be used to non-invasively detect APA in PA patients.

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Acknowledgments

We are grateful to Dr. Celso E. Gomez-Sanchez (Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi), who kindly provided us antibodies against CYP11B2.

Funding

This work was sponsored in part by the National Natural Science Foundation of China (Grant No. 81571713), CAMS Innovation Fund for Medical Sciences (CIFMS). Grant No. 2016-I2M-4-003, CAMS initiative for innovative medicine (No. CAMS-2018-I2M-3-001). The National Natural Science Foundation of China (81601529), the Tianjin Natural Science Foundation (18JCQNJC11600).

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Author notes

  1. Jie Ding and Yushi Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Jie Ding, Yaping Luo, Qingqing Pan, Wenjia Zhu, Xuezhu Wang & Li Huo

  2. Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, 100730, China

    Jie Ding, Yaping Luo, Qingqing Pan, Wenjia Zhu, Xuezhu Wang & Li Huo

  3. Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Yushi Zhang & Jin Wen

  4. Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Hui Zhang

  5. Department of Endocrinology and Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Huiping Wang & Anli Tong

  6. Department of Nuclear Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China

    Shaobo Yao

  7. Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany

    Michael C. Kreissl

  8. Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria

    Marcus Hacker & Xiang Li

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  1. Jie Ding
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Correspondence to Anli Tong or Li Huo.

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Conflict of interest

SCINTOMICS owns the IP on Pentixafor. All other authors declare that they have no conflict of interest.

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The clinical institutional review board approved this study.

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This article is part of the Topical Collection on Endocrinology

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Ding, J., Zhang, Y., Wen, J. et al. Imaging CXCR4 expression in patients with suspected primary hyperaldosteronism. Eur J Nucl Med Mol Imaging 47, 2656–2665 (2020). https://doi.org/10.1007/s00259-020-04722-0

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