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

  • Carlos Velasco
  • Adriana Mota-Cobián
  • Rubén A. Mota
  • Juan Pellico
  • Fernando Herranz
  • Carlos Galán-Arriola
  • Borja Ibáñez
  • Jesús Ruiz-Cabello
  • Jesús MateoEmail author
  • Samuel España
Original Article

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.

Keywords

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

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

Notes

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).

Supplementary material

12350_2019_1694_MOESM1_ESM.docx (38 kb)
Supplementary material 1 (DOCX 38 kb)
12350_2019_1694_MOESM2_ESM.pptx (3.3 mb)
Supplementary material 2 (PPTX 3387 kb)

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Copyright information

© American Society of Nuclear Cardiology 2019

Authors and Affiliations

  • Carlos Velasco
    • 1
    • 2
  • Adriana Mota-Cobián
    • 1
    • 2
  • Rubén A. Mota
    • 1
    • 3
  • Juan Pellico
    • 1
    • 8
  • Fernando Herranz
    • 1
    • 8
  • Carlos Galán-Arriola
    • 1
    • 4
  • Borja Ibáñez
    • 1
    • 4
    • 5
  • Jesús Ruiz-Cabello
    • 2
    • 6
    • 7
    • 8
  • Jesús Mateo
    • 1
    Email author
  • Samuel España
    • 1
    • 2
    • 9
  1. 1.Centro Nacional de Investigaciones Cardiovasculares (CNIC)MadridSpain
  2. 2.Universidad Complutense de MadridMadridSpain
  3. 3.Charles River Laboratories EspañaCerdanyolaSpain
  4. 4.CIBER de enfermedades CardiovascularesMadridSpain
  5. 5.Cardiology DepartmentIIS-Fundación Jiménez Díaz HospitalMadridSpain
  6. 6.CIC biomaGUNESan Sebastian-DonostiaSpain
  7. 7.IKERBASQUE, Basque Foundation for ScienceBilbaoSpain
  8. 8.CIBER de Enfermedades RespiratoriasMadridSpain
  9. 9.Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)MadridSpain

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