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Clinically relevant strategies for lowering cardiomyocyte glucose uptake for 18F-FDG imaging of myocardial inflammation in mice

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

Abstract

Purpose

Myocardial inflammation is an emerging target for novel therapies and thus for molecular imaging. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) has been employed, but requires an approach for suppression of cardiomyocyte uptake. We tested clinically viable strategies for their suitability in mouse models in order to optimize preclinical imaging protocols.

Methods

C57BL/6 mice (n = 56) underwent FDG PET under various conditions. In healthy animals, the effect of low-dose (5 units/kg) or high-dose (500 units/kg, 15 min prior) intravenous heparin, extended fasting (18 h) and the impact of conscious injection with limited, late application of isoflurane anaesthesia after 40 min of conscious uptake were examined in comparison to ketamine/xylazine anaesthesia. Conscious injection/uptake strategies were further evaluated at 3 days after permanent coronary artery occlusion.

Results

Under continuous isoflurane anaesthesia, neither heparin administration nor extended fasting significantly impacted myocardial 18F-FDG accumulation. Injection with 40 min uptake in awake mice resulted in a marked reduction of global myocardial 18F-FDG uptake compared to standard isoflurane anaesthesia (5.7 ± 1.1 %ID/g vs 30.2 ± 7.9 %ID/g, p < 0.01). Addition of heparin and fasting further reduced uptake compared to conscious injection alone (3.8 ± 1.5 %ID/g, p < 0.01) similar to ketamine/xylazine (2.4 ± 2.2 %ID/g, p < 0.001). In the inflammatory phase, 3 days after myocardial infarction, conscious injection/uptake with and without heparin/fasting identified a marked increase in myocardial 18F-FDG accumulation that was similar to that observed under ketamine/xylazine.

Conclusion

Continuous isoflurane anaesthesia obscures any suppressive effect of heparin or fasting on cardiomyocyte glucose utilization. Conscious injection of FDG in rodents significantly reduces cardiomyocyte uptake and enables further suppression by heparin and fasting, similar to clinical observations. In contrast to ketamine/xylazine, this represents a more physiological, translatable strategy for suppression of cardiomyocyte 18F-FDG uptake when targeting myocardial inflammation.

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Acknowledgments

The authors thank the preclinical molecular imaging and radiochemistry staff of the Department of Nuclear Medicine for their skilful technical assistance. JTT is supported by fellowships from the German Academic Exchange Service (DAAD) and the Canadian Institutes of Health Research. This project was partially funded by the REBIRTH-2 Cluster of Excellence and by EU FP7 grant PIRG08-GA-2010-276889 (FMB).

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Authors and Affiliations

  1. Department of Nuclear Medicine, Hanover Medical School, Carl Neuberg-Str. 1, 30625, Hanover, Germany

    James T. Thackeray, Jens P. Bankstahl & Frank M. Bengel

  2. Department of Cardiology and Angiology, Hanover Medical School, Carl Neuberg-Str. 1, 30625, Hanover, Germany

    Yong Wang & Kai C. Wollert

Authors
  1. James T. Thackeray
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  2. Jens P. Bankstahl
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  3. Yong Wang
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  4. Kai C. Wollert
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  5. Frank M. Bengel
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Correspondence to Frank M. Bengel.

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Thackeray, J.T., Bankstahl, J.P., Wang, Y. et al. Clinically relevant strategies for lowering cardiomyocyte glucose uptake for 18F-FDG imaging of myocardial inflammation in mice. Eur J Nucl Med Mol Imaging 42, 771–780 (2015). https://doi.org/10.1007/s00259-014-2956-7

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  • DOI: https://doi.org/10.1007/s00259-014-2956-7

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