Molecular imaging of inflammation crosstalk along the cardio-renal axis following acute myocardial infarction

Werner, Rudolf A.; Hess, Annika; Koenig, Tobias; Diekmann, Johanna; Derlin, Thorsten; Melk, Anette; Thackeray, James T.; Bauersachs, Johann; Bengel, Frank M.

doi:10.7150/thno.61423

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Theranostics 2021; 11(16):7984-7994. doi:10.7150/thno.61423 This issue Cite

Research Paper

Molecular imaging of inflammation crosstalk along the cardio-renal axis following acute myocardial infarction

Rudolf A. Werner^1✉, Annika Hess¹, Tobias Koenig², Johanna Diekmann¹, Thorsten Derlin¹, Anette Melk³, James T. Thackeray¹, Johann Bauersachs², Frank M. Bengel¹

1. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
2. Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
3. Department of Kidney, Liver and Metabolic Diseases, Children's Hospital, Hannover Medical School, Hannover, Germany.

Citation:

Werner RA, Hess A, Koenig T, Diekmann J, Derlin T, Melk A, Thackeray JT, Bauersachs J, Bengel FM. Molecular imaging of inflammation crosstalk along the cardio-renal axis following acute myocardial infarction. Theranostics 2021; 11(16):7984-7994. doi:10.7150/thno.61423. https://www.thno.org/v11p7984.htm

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Abstract

Rationale: Acute myocardial infarction (MI) triggers a systemic inflammatory response including crosstalk along the heart-kidney axis. We employed radionuclide-based inflammation-targeted whole-body molecular imaging to identify potential cardio-renal crosstalk after MI in a translational setup.

Methods: Serial whole-body positron emission tomography (PET) with the specific CXCR4 ligand ⁶⁸Ga-Pentixafor was performed after MI in mice. Tracer retention in kidneys and heart was compared to hematopoietic organs to evaluate systemic inflammation, validated by ex vivo analysis and correlated with progressive contractile dysfunction. Additionally, 96 patients underwent ⁶⁸Ga-Pentixafor PET within the first week after MI, for systems-based image analysis and to determine prognostic value for adverse renal outcome.

Results: In mice, transient myocardial CXCR4 upregulation occurred early after MI. Cardiac and renal PET signal directly correlated over the time course (r = 0.62, p < 0.0001), suggesting an inflammatory link between organs. Ex-vivo autoradiography (r = 0.9, p < 0.01) and CD68 immunostaining indicated signal localization to inflammatory cell content. Renal signal at 7d was inversely proportional to left ventricular ejection fraction at 6 weeks after MI (r = -0.79, p < 0.01). In patients, renal CXCR4 signal also correlated with signal from infarct (r = 0.25, p < 0.05) and remote myocardium (r = 0.39, p < 0.0001). Glomerular filtration rate (GFR) was available in 48/96 (50%) during follow-up. Worsening of renal function (GFR loss >5 mL/min/1.73m²), occurred a mean 80.5 days after MI in 16/48 (33.3%). Kaplan-Meier analysis revealed adverse renal outcome for patients with elevated remote myocardial CXCR4 signal (p < 0.05). Multivariate Cox analysis confirmed an independent predictive value (relative to baseline GFR, LVEF, infarct size; HR, 5.27).

Conclusion: Systems-based CXCR4-targeted molecular imaging identifies inflammatory crosstalk along the cardio-renal axis early after MI.

Keywords: Cardiorenal syndrome, myocardial infarction, molecular imaging, CXCR4, inflammation

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APA

Werner, R.A., Hess, A., Koenig, T., Diekmann, J., Derlin, T., Melk, A., Thackeray, J.T., Bauersachs, J., Bengel, F.M. (2021). Molecular imaging of inflammation crosstalk along the cardio-renal axis following acute myocardial infarction. Theranostics, 11(16), 7984-7994. https://doi.org/10.7150/thno.61423.

ACS

Werner, R.A.; Hess, A.; Koenig, T.; Diekmann, J.; Derlin, T.; Melk, A.; Thackeray, J.T.; Bauersachs, J.; Bengel, F.M. Molecular imaging of inflammation crosstalk along the cardio-renal axis following acute myocardial infarction. Theranostics 2021, 11 (16), 7984-7994. DOI: 10.7150/thno.61423.

NLM

CSE

Werner RA, Hess A, Koenig T, Diekmann J, Derlin T, Melk A, Thackeray JT, Bauersachs J, Bengel FM. 2021. Molecular imaging of inflammation crosstalk along the cardio-renal axis following acute myocardial infarction. Theranostics. 11(16):7984-7994.

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