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Feasibility study of PET dynamic imaging of [18F]DHMT for quantification of reactive oxygen species in the myocardium of large animals

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Journal of Nuclear Cardiology Aims and scope

Abstract

Objectives

We aimed to develop a dynamic imaging technique for a novel PET superoxide tracer, [18F]DHMT, to allow for absolute quantification of myocardial reactive oxygen species (ROS) production in a large animal model.

Methods

Six beagle dogs underwent a single baseline dynamic [18F]DHMT PET study, whereas one animal underwent three serial dynamic studies over the course of chronic doxorubicin administration (1 mg·kg−1·week−1 for 15 weeks). During the scans, sequential arterial blood samples were obtained for plasma metabolite correction. The optimal compartment model and graphical analysis method were identified for kinetic modeling. Values for the left ventricular (LV) net influx rate, Ki, were reported for all the studies and compared with the LV standard uptake values (SUVs) and the LV-to-blood pool SUV ratios from the 60 to 90 minute static images. Parametric images were also generated.

Results

[18F]DHMT followed irreversible kinetics once oxidized within the myocardium in the presence of superoxide, as evidenced by the fitting generated by the irreversible two-tissue (2Ti) compartment model and the linearity of Patlak analysis. Myocardial Ki values showed a weak correlation with LV SUV (R2 = 0.27), but a strong correlation with LV-to-blood pool SUV ratio (R2 = 0.92). Generation of high-quality parametric images showed superior myocardial to blood contrast compared to static images.

Conclusions

A dynamic PET imaging technique for [18F]DHMT was developed with full and simplified kinetic modeling for absolute quantification of myocardial superoxide production in a large animal model.

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Abbreviations

ROS:

Reactive oxygen species

[18F]DHMT:

[18F]-6-(4-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-methyl-5, 6-dihydrophenanthridine-3, 8-diamine

VOI:

Volume of interest

TAC:

Time activity curve

SUV:

Standard uptake value

2Ti:

Two-tissue irreversible

DOX:

Doxorubicin

LVEF:

Left ventricular ejection fraction

K i :

Net influx rate

AIC:

Akaike information criterion

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Acknowledgments

We would like to thank Dr. Eva Romito, Tsa Shelton and Christi Hawley for their participation and support of the animal studies.

Disclosure

The authors declare that they have no conflict of interest.

Author information

Author notes

  1. Jing Wu and Nabil E. Boutagy contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology and Biomedical Imaging, Yale School of Medicine, PO Box 208048, New Haven, CT, 06520-8048, USA

    Jing Wu PhD, Zhengxin Cai PhD, Shu-fei Lin PhD, Ming-Qiang Zheng PhD, Michael Kapinos BS, Jean-Dominique Gallezot PhD, Hui Liu PhD, Tim Mulnix PhD, Wenjie Zhang MD, PhD, Marcel Lindemann PhD, Jo-ku Teng MS, Yiyun Huang PhD, Richard E. Carson PhD, Albert J. Sinusas MD & Chi Liu PhD

  2. Section of Cardiovascular Medicine, Department of Medicine, Yale Translational Research Imaging Center, Yale School of Medicine, New Haven, CT, USA

    Nabil E. Boutagy PhD, Attila Feher MD, PhD, John C. Stendahl MD, PhD, Edward J. Miller MD, PhD & Albert J. Sinusas MD

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  1. Jing Wu PhD
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  2. Nabil E. Boutagy PhD
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  18. Albert J. Sinusas MD
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  19. Chi Liu PhD
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Corresponding author

Correspondence to Chi Liu PhD.

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Funding

This work is supported by an internal funding from the Department of Radiology and Biomedical Imaging at Yale University, and the NIH grants R01HL123949 and T32HL098069.

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Wu, J., Boutagy, N.E., Cai, Z. et al. Feasibility study of PET dynamic imaging of [18F]DHMT for quantification of reactive oxygen species in the myocardium of large animals. J. Nucl. Cardiol. 29, 216–225 (2022). https://doi.org/10.1007/s12350-020-02184-3

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  • DOI: https://doi.org/10.1007/s12350-020-02184-3

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