Quantitative assessment of myocardial blood flow and extracellular volume fraction using 68Ga-DOTA-PET: A feasibility and validation study in large animals

Abstract

Background

Here we evaluated the feasibility of PET with Gallium-68 (68Ga)-labeled DOTA for non-invasive assessment of myocardial blood flow (MBF) and extracellular volume fraction (ECV) in a pig model of myocardial infarction. We also aimed to validate MBF measurements using microspheres as a gold standard in healthy pigs.

Methods

8 healthy pigs underwent three sequential 68Ga-DOTA-PET/CT scans at rest and during pharmacological stress with simultaneous injection of fluorescent microspheres to validate MBF measurements. Myocardial infarction was induced in 5 additional pigs, which underwent 68Ga-DOTA-PET/CT examinations 7-days after reperfusion. Dynamic PET images were reconstructed and fitted to obtain MBF and ECV parametric maps.

Results

MBF assessed with 68Ga-DOTA-PET showed good correlation (y = 0.96x + 0.11, r = 0.91) with that measured with microspheres. MBF values obtained with 68Ga-DOTA-PET in the infarcted area (LAD, left anterior descendant) were significantly reduced in comparison to remote ones LCX (left circumflex artery, P < 0.0001) and RCA (right coronary artery, P < 0.0001). ECV increased in the infarcted area (P < 0.0001).

Conclusion

68Ga-DOTA-PET allowed non-invasive assessment of MBF and ECV in pigs with myocardial infarction and under rest-stress conditions. This technique could provide wide access to quantitative measurement of both MBF and ECV with PET imaging.

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Abbreviations

CAD:

Coronary artery disease

CGS-21680:

2-p-(2-Carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine

CMR:

Cardiac magnetic resonance

CT:

Computed tomography

DOTA:

1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid

ECV:

Extracellular volume fraction

MBF:

Myocardial blood flow

MS:

Microspheres

PET:

Positron emission tomography

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Acknowledgments

The authors would like to thank Dr. Stuart Pocock (London School of Hygiene and Tropical Medicine, UK) for his help and advice regarding statistical analysis.

Disclosure

All authors have reported that they have no relationships relevant to the contents of this paper to disclose. This work was supported by grants from the Ministerio de Economía, Industria y Competitividad (MEIC) (SAF2014-58920-R), from the Carlos III Institute of Health of Spain and Fondo Europeo de Desarrollo Regional (FEDER, “Una manera de hacer Europa”) (FIS-FEDER PI14-01427), and from the Comunidad de Madrid (2016-T1/TIC-1099). C. Velasco holds a fellowship from the Spanish Ministry of Education (FPU014/01794). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (MDM-2017-0720).

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Correspondence to Jesús Mateo PhD.

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Velasco, C., Mota-Cobián, A., Mota, R.A. et al. Quantitative assessment of myocardial blood flow and extracellular volume fraction using 68Ga-DOTA-PET: A feasibility and validation study in large animals. J. Nucl. Cardiol. (2019). https://doi.org/10.1007/s12350-019-01694-z

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Keywords

  • PET
  • myocardial blood flow
  • perfusion agents
  • tracers
  • molecular imaging agents
  • molecular imaging