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Functional nodules in primary aldosteronism: identification of CXCR4 expression with 68Ga-pentixafor PET/CT

  • Molecular Imaging
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Abstract

Objectives

We analyzed the diagnostic efficiency of 68Ga-pentixafor PET/CT for functional nodules in primary aldosteronism (PA). Furthermore, we compared the correlation of CXCR4 expression with aldosterone synthase (CYP11B2) expression and PET/CT uptake in these patients.

Methods

We prospectively assessed 50 patients diagnosed with PA and 10 patients with non-functional adrenal adenoma (NFA). All patients underwent 68Ga-pentixafor PET/CT before adrenalectomy. Immunohistochemistry (IHC) was performed to detect the protein expression of CYP11B2 and the G-protein-coupled receptor CXCR4.

Results

CYP11B2 IHC revealed the presence of 43 functional nodules. Subsequently, 40/43 functional nodules could be detected on 68Ga-pentixafor PET/CT, while negative imaging findings were noted for 11/13 non-functional nodules (sensitivity, 93.0%; specificity, 84.6%). The optimum SUVmax cut-off for the identification of functional nodules was 8.95 (AUC 0.914 [0.828–1.000], p < 0.001). Regarding the size of functional nodules, diagnostic efficiency appeared to be much higher for nodules greater than 1 cm in size (sensitivity, up to 97.3%). Moreover, we examined the relationship between CXCR4 and CYP11B2 expression in 56 lesions. All 43 CYP11B2-positive nodules were CXCR4-positive, but one of the 13 CYP11B2-negative nodules (7.7%) showed false-positive staining for CXCR4. Moreover, the consistency between PET/CT uptake and CXCR4 staining results was 92.9% (52/56).

Conclusions

At least 90% of functional nodules show positive uptake on 68Ga-pentixafor PET/CT, and the detection ability is much better for nodules with a diameter ≥ 1 cm. With its high sensitivity and specificity, 68Ga-pentixafor PET/CT can be considered a promising surgical decision-making tool for patients with PA.

Key Points

• 68Ga-pentixafor PET/CT could be a useful tool for the identification of functional adrenal nodules in APAs and even IHAs.

• The diagnostic efficiency appears to be much higher for nodules ≥ 1 cm in size.

• There is high consistency between the results of 68Ga-pentixafor PET/CT imaging and CXCR4 immunohistochemistry.

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Abbreviations

APA:

Aldosterone-producing adenoma

APM:

Aldosterone-producing micronodule

ARR:

Aldosterone-to-renin ratio

AVS:

Adrenal venous sampling

CYP11B2:

Aldosterone synthase

IHA:

Idiopathic hyperaldosteronism

IHC:

Immunohistochemistry

NFA:

Non-functional adrenal adenoma

NPV:

Negative predictive value

PA:

Primary aldosteronism

PET/CT:

Positron emission tomography/computed tomography

PPV:

Positive predictive value

ROC:

Receiver-operating characteristic

SUVmax :

The maximum standardized uptake values

ZG:

Zona glomerulosa

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Acknowledgements

We are grateful to Dr. Celso E. Gomez-Sanchez (Department of Medicine, University of Mississippi Medical Center, Jackson, MS), who kindly provided antibodies against CYP11B2. Furthermore, we would like to thank all the reviewers who participated in the review and MJEditor (www.mjeditor.com) for linguistic assistance during the preparation of this manuscript. Anli Tong is deemed to take overall responsibility for all aspects of the study (ethics, consent, data handling and storage, and all other aspects of Good Research Practice). This research was funded by the National Natural Science Foundation of China (Grant Nos. 81770427 and 82070822). The study received ethical approval from the ethics committee of Peking Union Medical College Hospital (IRB protocol #ZS-1435).

Funding

This study has received funding by the National Natural Science Foundation of China (Grant Nos. 81770427 and 82070822).

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Authors and Affiliations

  1. NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital); Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Dongcheng, Beijing, 100730, China

    Yinjie Gao, Yunying Cui, Tianyi Li & Anli Tong

  2. Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine and State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Science and PUMC, Beijing, 100730, China

    Jie Ding & Li Huo

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

    Hao Sun

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

    Dachun Zhao

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

    Yushi Zhang

Authors
  1. Yinjie Gao
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  2. Jie Ding
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  3. Yunying Cui
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  4. Tianyi Li
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  7. Yushi Zhang
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  8. Li Huo
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  9. Anli Tong
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Corresponding authors

Correspondence to Yushi Zhang, Li Huo or Anli Tong.

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Guarantor

The scientific guarantor of this publication is Anli Tong.

Conflict of interest

The authors declare no competing interests.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained (IRB protocol #ZS-1435).

Methodology

• retrospective

• diagnostic or prognostic study

• performed at one institution

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Yinjie Gao and Jie Ding are co-first authors.

Supplementary information

Table S1.

Clinical characteristic of enrolled patients *ARR ([ng/dl]/[ng/ml/h]) = Plasma aldosterone concentration (ng/dl) / Renin activity (ng/ml/h). When the renin activity was lower than 0.2 ng/ml/h, the ARR was calculated using 0.2 as the denominator. Quantitative variables with normal distribution are expressed as means ± standard deviations, and other quantitative variables are expressed as median (quartile). *Four APA patients with bilateral lesions underwent unilateral operation eventually according to the results of 68Ga-pentixafor PET/CT, of which the lesions with positive imaging were removed. (PDF 33 kb)

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Gao, Y., Ding, J., Cui, Y. et al. Functional nodules in primary aldosteronism: identification of CXCR4 expression with 68Ga-pentixafor PET/CT. Eur Radiol 33, 996–1003 (2023). https://doi.org/10.1007/s00330-022-09058-x

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