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[\({}^{11}\hbox {C}\)]acetate and PET/CT assessment of muscle activation in rat studies

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Abstract

Purpose

The purpose of the present study is to apply kinetic analysis to investigate exercise-related changes in the metabolism of the skeletal muscle of the rat hindlimb by [\({}^{11}\hbox {C}\)]acetate positron emission tomography and computed tomography (PET/CT).

Methods

Contractions were induced in Wistar rats’ left hindlimb by electrostimulation of the Vastus Lateralis muscle motor point. After 15 min of muscle contractions, [\({}^{11}\hbox {C}\)]acetate was injected and PET/CT of both hindlimbs was acquired. The resting hindlimb was used as a control reference. The kinetic parameters \(K_1\) and \(k_2\) were calculated for the target muscles (exercised and control) and correlated with the corresponding standardized uptake values (SUVs). The ratio between each kinetic parameter values and the SUV extracted for the exercised muscle and the muscle at rest was computed (\(K_1^{Ex}/K_1^{Re},\, k_2^{Ex}/k_2^{Re}\) and \(\hbox {SUV}^{Ex}/\hbox {SUV}^{Re}\), respectively).

Results

Kinetic analysis quantitatively confirmed that net tracer uptake (\(K_1\)) and washout (\(k_2\)) were significantly higher in exercised muscles (\(K_1: \,0.34 \pm 0.12 \hbox { min}^{-1}\) for exercised muscles vs. \(0.18 \pm 0.09\hbox { min}^{-1}\) for resting muscles, \(P=0.01\); \(k_2:\, 0.22 \pm 0.05\hbox { min}^{-1}\) for exercised muscle vs. \(0.14 \pm 0.04 \hbox { min}^{-1}\) for resting muscle, \(P=0.002\)). On the other hand, SUV was not significantly different between active and inactive muscles (\(0.7 \pm 0.2\) for exercised muscles vs. \(0.6 \pm 0.1\) for resting muscles). Linear regression analysis revealed a good correlation (\(R^2=0.75,\, P=0.005\)) between net tracer uptake ratio (\(K_1^{Ex}/K_1^{Re}\)) and the SUV ratio \((\hbox {SUV}^{Ex}/\hbox {SUV}^{Re}\)). A lower correlation was found between the net tracer washout ratio (\(k_2^{Ex}/k_2^{Re}\)) and the SUV ratio (\(R^2=0.37,\, P=0.1\)).

Conclusion

The present study showed that kinetic modelling can detect changes between active and inactive skeletal muscles with a higher sensitivity with respect to the SUV, when performed with [\({}^{11}\hbox {C}\)]acetate PET/CT.

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Notes

  1. This approach is generally preferred in patients, because of the invasiveness of arterial sampling. However, these methods may offer limited accuracy, require complex correcting factors and lack the necessary temporal resolution.

  2. Moreover, clinically feasible model-fitting algorithm have recently been applied on whole-body dynamic PET human studies [24]

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Acknowledgments

This work was supported by the European Marie-Curie project Multiscale Biological Modalities for Physiological Human Articulation (MSH - Grant Agreement: 289897), and by the Centre for Biomedical Imaging (CIBM), Geneva, CH. Many thanks are due to Prof. Daniel Huber (Huberlab, Department of Fundamental Neurosciences, University Medical Centre (CMU), Geneva, CH) for kindly providing part of the laboratory equipment.

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Authors and Affiliations

  1. University of Geneva and University Hospitals of Geneva, 4 Rue Gabrielle-Perret-Gentil, 1211, Geneva 14, Switzerland

    Sara Trombella & David García

  2. University Hospitals of Geneva and Centre for Biomedical Imaging (CIBM), 4 Rue Gabrielle-Perret-Gentil, 1211, Geneva 14, Switzerland

    Didier J. Colin & Stéphane Germain

  3. University Hospitals of Geneva, 4 Rue Gabrielle-Perret-Gentil, 1211, Geneva 14, Switzerland

    Yann Seimbille & Osman Ratib

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  1. Sara Trombella
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Correspondence to Sara Trombella.

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Sara Trombella, David García, Didier J. Colin, Stéphane Germain, Yann Seimbille and Osman Ratib declare no conflicts of interest.

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All institutional and national guidelines for the care and use of laboratory animals were followed.

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Trombella, S., García, D., Colin, D.J. et al. [\({}^{11}\hbox {C}\)]acetate and PET/CT assessment of muscle activation in rat studies. Int J CARS 11, 733–743 (2016). https://doi.org/10.1007/s11548-015-1260-8

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  • DOI: https://doi.org/10.1007/s11548-015-1260-8

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