Skip to main content
Top
Published in: EJNMMI Research 1/2021

Open Access 01-12-2021 | Positron Emission Tomography | Original research

Comparison of metabolic and functional parameters using cardiac 18F-FDG-PET in early to mid-adulthood male and female mice

Authors: Maximilian Fischer, Mathias J. Zacherl, Tobias Weinberger, Ludwig Weckbach, Bruno Huber, Christian Schulz, Steffen Massberg, Peter Bartenstein, Sebastian Lehner, Andrei Todica

Published in: EJNMMI Research | Issue 1/2021

Login to get access

Abstract

Background

In this descriptive study of male and female mice at different weeks of age, we use serial non-invasive cardiac 18F-FDG-PET scans to follow up on metabolic alterations, heart function parameters, and the ECG of both sexes in early to mid-adulthood.

Methods

ECG-gated 18F-FDG-PET scans were performed in mice on 10, 14, and 18 weeks of age, using a dedicated small-animal PET scanner. The percentage of the injected activity per gram (%IA/g) in the heart, left ventricular metabolic volume (LVMV), myocardial viability and left ventricular function parameters: end-diastolic (EDV), end-systolic (ESV), stroke volume (SV), and the ejection fraction (EF%) were estimated.

Results

Compared to their age-matched female counterpart, male mice showed a constant increase in LVMV and ventricular volume during the follow-up. In contrast, female mice remain stable after ten weeks of age. Furthermore, male mice showed lower heart rates, positive correlation with cardiac %IA/g, and negative correlation with LVMV.

Conclusion

In this study of serial cardiac PET scans, we provide insight for basic murine research models, showing that mice gender and age show distinct cardiac metabolisms. These physiologic alterations need to be considered when planning in vivo injury models to avoid potential pitfalls.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016;37:2129–2200m.CrossRef Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016;37:2129–2200m.CrossRef
3.
go back to reference Ramanujam D, Sassi Y, Laggerbauer B, Engelhardt S. Viral vector-based targeting of miR-21 in cardiac nonmyocyte cells reduces pathologic remodeling of the heart. Mol Ther [Internet]. 2016;24:1939–48.CrossRef Ramanujam D, Sassi Y, Laggerbauer B, Engelhardt S. Viral vector-based targeting of miR-21 in cardiac nonmyocyte cells reduces pathologic remodeling of the heart. Mol Ther [Internet]. 2016;24:1939–48.CrossRef
4.
go back to reference Patten RD. Models of gender differences in cardiovascular disease. Drug Discov Today Dis Model [Internet]. 2007;4:227–32.CrossRef Patten RD. Models of gender differences in cardiovascular disease. Drug Discov Today Dis Model [Internet]. 2007;4:227–32.CrossRef
5.
go back to reference Du X. Gender modulates cardiac phenotype development in genetically modified mice. Cardiovasc Res [Internet]. 2004;63:510–9.CrossRef Du X. Gender modulates cardiac phenotype development in genetically modified mice. Cardiovasc Res [Internet]. 2004;63:510–9.CrossRef
6.
go back to reference Delbeck M. Impaired left-ventricular cardiac function in male GPR30-deficient mice. Mol Med Rep [Internet]. 2010;4:37–40.PubMed Delbeck M. Impaired left-ventricular cardiac function in male GPR30-deficient mice. Mol Med Rep [Internet]. 2010;4:37–40.PubMed
7.
go back to reference Cross HR, Lu L, Steenbergen C, Philipson KD, Murphy E. Overexpression of the cardiac Na + /Ca 2+ exchanger increases susceptibility to ischemia/reperfusion injury in male, but not female, transgenic mice. Circ Res [Internet]. 1998;83:1215–23.CrossRef Cross HR, Lu L, Steenbergen C, Philipson KD, Murphy E. Overexpression of the cardiac Na + /Ca 2+ exchanger increases susceptibility to ischemia/reperfusion injury in male, but not female, transgenic mice. Circ Res [Internet]. 1998;83:1215–23.CrossRef
8.
go back to reference Bowden MA, Tesch GH, Julius TL, Rosli S, Love JE, Ritchie RH. Earlier onset of diabesity-Induced adverse cardiac remodeling in female compared to male mice. Obesity [Internet]. 2015;23:1166–77.CrossRef Bowden MA, Tesch GH, Julius TL, Rosli S, Love JE, Ritchie RH. Earlier onset of diabesity-Induced adverse cardiac remodeling in female compared to male mice. Obesity [Internet]. 2015;23:1166–77.CrossRef
9.
go back to reference Lang C, Lehner S, Todica A, Boening G, Franz W-M, Bartenstein P, et al. Positron emission tomography based in-vivo imaging of early phase stem cell retention after intramyocardial delivery in the mouse model. Eur J Nucl Med Mol Imaging [Internet]. 2013;40:1730–8.CrossRef Lang C, Lehner S, Todica A, Boening G, Franz W-M, Bartenstein P, et al. Positron emission tomography based in-vivo imaging of early phase stem cell retention after intramyocardial delivery in the mouse model. Eur J Nucl Med Mol Imaging [Internet]. 2013;40:1730–8.CrossRef
10.
go back to reference Croteau E, Bénard F, Cadorette J, Gauthier ME, Aliaga A, Bentourkia M, et al. Quantitative gated PET for the assessment of left ventricular function in small animals. J Nucl Med. 2003;44:1655–61.PubMed Croteau E, Bénard F, Cadorette J, Gauthier ME, Aliaga A, Bentourkia M, et al. Quantitative gated PET for the assessment of left ventricular function in small animals. J Nucl Med. 2003;44:1655–61.PubMed
11.
go back to reference Todica A, Zacherl MJ, Wang H, Böning G, Jansen NL, Wängler C, et al. In-vivo monitoring of erythropoietin treatment after myocardial infarction in mice with [68Ga]Annexin A5 and [18F]FDG PET. J Nucl Cardiol [Internet]. 2014;21:1191–9.CrossRef Todica A, Zacherl MJ, Wang H, Böning G, Jansen NL, Wängler C, et al. In-vivo monitoring of erythropoietin treatment after myocardial infarction in mice with [68Ga]Annexin A5 and [18F]FDG PET. J Nucl Cardiol [Internet]. 2014;21:1191–9.CrossRef
12.
go back to reference Brunner S, Todica A, Böning G, Nekolla SG, Wildgruber M, Lehner S, et al. Left ventricular functional assessment in murine models of ischemic and dilated cardiomyopathy using [18 F]FDG-PET: comparison with cardiac MRI and monitoring erythropoietin therapy. EJNMMI Res [Internet]. 2012;2:43.CrossRef Brunner S, Todica A, Böning G, Nekolla SG, Wildgruber M, Lehner S, et al. Left ventricular functional assessment in murine models of ischemic and dilated cardiomyopathy using [18 F]FDG-PET: comparison with cardiac MRI and monitoring erythropoietin therapy. EJNMMI Res [Internet]. 2012;2:43.CrossRef
13.
go back to reference Todica A, Beetz NL, Günther L, Zacherl MJ, Grabmaier U, Huber B, et al. Monitoring of cardiac remodeling in a mouse model of pressure-overload left ventricular hypertrophy with [18F]FDG MicroPET. Mol Imaging Biol. 2018;20:268–74.CrossRef Todica A, Beetz NL, Günther L, Zacherl MJ, Grabmaier U, Huber B, et al. Monitoring of cardiac remodeling in a mouse model of pressure-overload left ventricular hypertrophy with [18F]FDG MicroPET. Mol Imaging Biol. 2018;20:268–74.CrossRef
14.
go back to reference Gross L, Paintmayer L, Lehner S, Brandl L, Brenner C, Grabmaier U, et al. FDG-PET reveals improved cardiac regeneration and attenuated adverse remodelling following Sitagliptin 1 G-CSF therapy after acute myocardial infarction. Eur Heart J Cardiovasc Imaging [Internet]. 2016;17:136–45.CrossRef Gross L, Paintmayer L, Lehner S, Brandl L, Brenner C, Grabmaier U, et al. FDG-PET reveals improved cardiac regeneration and attenuated adverse remodelling following Sitagliptin 1 G-CSF therapy after acute myocardial infarction. Eur Heart J Cardiovasc Imaging [Internet]. 2016;17:136–45.CrossRef
15.
go back to reference Greco A, Petretta MP, Larobina M, Gargiulo S, Panico M, Nekolla SG, et al. Reproducibility and accuracy of non-invasive measurement of infarct size in mice with high-resolution PET/CT. J Nucl Cardiol. 2012;19:492–9.CrossRef Greco A, Petretta MP, Larobina M, Gargiulo S, Panico M, Nekolla SG, et al. Reproducibility and accuracy of non-invasive measurement of infarct size in mice with high-resolution PET/CT. J Nucl Cardiol. 2012;19:492–9.CrossRef
16.
go back to reference Fueger BJ, Czernin J, Hildebrandt I, Tran C, Halpern BS, Stout D, et al. Impact of animal handling on the results of 18F-FDG PET studies in mice. J Nucl Med [Internet]. 2006;47:999–1006.PubMed Fueger BJ, Czernin J, Hildebrandt I, Tran C, Halpern BS, Stout D, et al. Impact of animal handling on the results of 18F-FDG PET studies in mice. J Nucl Med [Internet]. 2006;47:999–1006.PubMed
17.
go back to reference Kreissl MC, Stout DB, Wong K-P, Wu H-M, Caglayan E, Ladno W, et al. Influence of dietary state and insulin on myocardial, skeletal muscle and brain [18F]-fluorodeoxyglucose kinetics in mice. EJNMMI Res [Internet]. Springer Open Ltd; 2011;1:8. http://www.ejnmmires.com/content/1/1/8 Kreissl MC, Stout DB, Wong K-P, Wu H-M, Caglayan E, Ladno W, et al. Influence of dietary state and insulin on myocardial, skeletal muscle and brain [18F]-fluorodeoxyglucose kinetics in mice. EJNMMI Res [Internet]. Springer Open Ltd; 2011;1:8. http://​www.​ejnmmires.​com/​content/​1/​1/​8
18.
go back to reference Thackeray JT, Bankstahl JP, Wang Y, Wollert KC, Bengel FM. Clinically relevant strategies for lowering cardiomyocyte glucose uptake for 18F-FDG imaging of myocardial inflammation in mice. Eur J Nucl Med Mol Imaging [Internet]. 2015;42:771–80.CrossRef Thackeray JT, Bankstahl JP, Wang Y, Wollert KC, Bengel FM. Clinically relevant strategies for lowering cardiomyocyte glucose uptake for 18F-FDG imaging of myocardial inflammation in mice. Eur J Nucl Med Mol Imaging [Internet]. 2015;42:771–80.CrossRef
19.
go back to reference Toyama H, Ichise M, Liow J-S, Vines DC, Seneca NM, Modell KJ, et al. Evaluation of anesthesia effects on [18F]FDG uptake in mouse brain and heart using small animal PET. Nucl Med Biol [Internet]. 2004;31:251–6.CrossRef Toyama H, Ichise M, Liow J-S, Vines DC, Seneca NM, Modell KJ, et al. Evaluation of anesthesia effects on [18F]FDG uptake in mouse brain and heart using small animal PET. Nucl Med Biol [Internet]. 2004;31:251–6.CrossRef
20.
go back to reference Todica A, Brunner S, Böning G, Lehner S, Nekolla SG, Wildgruber M, et al. [68Ga]-albumin-PET in the monitoring of left ventricular function in murine models of ischemic and dilated cardiomyopathy: comparison with cardiac MRI. Mol Imaging Biol [Internet]. 2013;15:441–9.CrossRef Todica A, Brunner S, Böning G, Lehner S, Nekolla SG, Wildgruber M, et al. [68Ga]-albumin-PET in the monitoring of left ventricular function in murine models of ischemic and dilated cardiomyopathy: comparison with cardiac MRI. Mol Imaging Biol [Internet]. 2013;15:441–9.CrossRef
21.
go back to reference Böning G, Todica A, Vai A, Lehner S, Xiong G, Mille E, et al. Erroneous cardiac ECG-gated PET list-mode trigger events can be retrospectively identified and replaced by an offline reprocessing approach: first results in rodents. Phys Med Biol [Internet]. 2013;58:7937–59.CrossRef Böning G, Todica A, Vai A, Lehner S, Xiong G, Mille E, et al. Erroneous cardiac ECG-gated PET list-mode trigger events can be retrospectively identified and replaced by an offline reprocessing approach: first results in rodents. Phys Med Biol [Internet]. 2013;58:7937–59.CrossRef
22.
go back to reference Todica A, Siebermair J, Schiller J, Zacherl MJ, Fendler WP, Massberg S, et al. Assessment of right ventricular sympathetic dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy: An 123I-metaiodobenzylguanidine SPECT/CT study. J Nucl Cardiol [Internet]. 2018; https://doi.org/10.1007/s12350-018-01545-3 Todica A, Siebermair J, Schiller J, Zacherl MJ, Fendler WP, Massberg S, et al. Assessment of right ventricular sympathetic dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy: An 123I-metaiodobenzylguanidine SPECT/CT study. J Nucl Cardiol [Internet]. 2018; https://​doi.​org/​10.​1007/​s12350-018-01545-3
23.
go back to reference Luczak ED, Leinwand LA. Sex-based cardiac physiology. Annu Rev Physiol [Internet]. 2009;71:1–18.CrossRef Luczak ED, Leinwand LA. Sex-based cardiac physiology. Annu Rev Physiol [Internet]. 2009;71:1–18.CrossRef
24.
go back to reference Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol [Internet]. 2018;15:387–407.CrossRef Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol [Internet]. 2018;15:387–407.CrossRef
25.
go back to reference Thackeray JT, Bankstahl JP, Wang Y, Korf-Klingebiel M, Walte A, Wittneben A, et al. Targeting post-infarct inflammation by PET imaging: comparison of (68)Ga-citrate and (68)Ga-DOTATATE with (18)F-FDG in a mouse model. Eur J Nucl Med Mol Imaging [Internet]. 2015;42:317–27.CrossRef Thackeray JT, Bankstahl JP, Wang Y, Korf-Klingebiel M, Walte A, Wittneben A, et al. Targeting post-infarct inflammation by PET imaging: comparison of (68)Ga-citrate and (68)Ga-DOTATATE with (18)F-FDG in a mouse model. Eur J Nucl Med Mol Imaging [Internet]. 2015;42:317–27.CrossRef
Metadata
Title
Comparison of metabolic and functional parameters using cardiac 18F-FDG-PET in early to mid-adulthood male and female mice
Authors
Maximilian Fischer
Mathias J. Zacherl
Tobias Weinberger
Ludwig Weckbach
Bruno Huber
Christian Schulz
Steffen Massberg
Peter Bartenstein
Sebastian Lehner
Andrei Todica
Publication date
01-12-2021
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2021
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-021-00748-z

Other articles of this Issue 1/2021

EJNMMI Research 1/2021 Go to the issue