Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs

Miikka Tarkia, Antti Saraste, Tiina Saanijoki, Vesa Oikonen, Tommi Vähäsilta, Marjatta Strandberg, Christoffer Stark, Tuula Tolvanen, Mika Teräs, Timo Savunen, Mark A. Green, Juhani Knuuti, Anne Roivainen

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose: We evaluated four potential gallium-68 ( 68Ga)-labeled tracers for positron emission tomography (PET) imaging of myocardial perfusion in comparison with oxygen-15-labeled water ([ 15O]water) in healthy pigs. Four hexadentate salicylaldimine ligands derived from bis(3-aminopropyl)ethylenediamine (BAPEN) that showed promise in previous rat experiments were selected for this study. Methods: Following an evaluation of myocardial blood flow with [ 15O]water PET, the pigs (total n=14) underwent a dynamic 90-min PET study with one of four 68Ga-labeled BAPEN derivatives (n=3-5 per tracer) either at rest or under adenosine stress. Serial arterial blood samples were collected during the imaging for the measurements of total radioactivity, radiometabolites, plasma protein binding and blood-to-plasma ratio for the 68Ga chelates. Time-activity curves of the left ventricular blood pool and myocardium were derived from PET images, and metabolite-corrected arterial input function was used for kinetic modeling. Also, ex vivo biodistribution of 68Ga radioactivity was analyzed. Results: All four 68Ga tracers showed undesirably slow myocardial accumulation over time, but their in vivo stability, clearance from blood and the kinetics of the myocardium uptake varied. [ 68Ga][Ga-(sal) 2BAPDMEN] 1+ showed the highest myocardial uptake in PET images and tissue samples (myocardium-to-blood ratio 7.63±1.89, myocardium-to-lung ratio 3.03±0.33 and myocardium-to-liver ratio 1.80±0.82). However, there was no correlation between the myocardial perfusion measured with [ 15O]water and the net uptake rates or K 1 values of the 68Ga chelates. Conclusion: Our results revealed that myocardial accumulation of the 68Ga chelates proposed for myocardial perfusion imaging with PET was slow and not determined by myocardial perfusion in a large animal model. These findings suggest that the studied tracers are not suitable for clinical imaging of myocardial perfusion.

Original languageEnglish (US)
Pages (from-to)715-723
Number of pages9
JournalNuclear Medicine and Biology
Volume39
Issue number5
DOIs
StatePublished - Jul 1 2012

Fingerprint

Myocardial Perfusion Imaging
Positron-Emission Tomography
ethylenediamine
Swine
Myocardium
Water
Radioactivity
Perfusion
Gallium
Protein Binding
Adenosine
Blood Proteins
Animal Models
Oxygen
Ligands
Lung
Liver

Keywords

  • Gallium-68
  • Myocardial perfusion
  • Positron emission tomography

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Tarkia, M., Saraste, A., Saanijoki, T., Oikonen, V., Vähäsilta, T., Strandberg, M., ... Roivainen, A. (2012). Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs. Nuclear Medicine and Biology, 39(5), 715-723. https://doi.org/10.1016/j.nucmedbio.2011.11.007

Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs. / Tarkia, Miikka; Saraste, Antti; Saanijoki, Tiina; Oikonen, Vesa; Vähäsilta, Tommi; Strandberg, Marjatta; Stark, Christoffer; Tolvanen, Tuula; Teräs, Mika; Savunen, Timo; Green, Mark A.; Knuuti, Juhani; Roivainen, Anne.

In: Nuclear Medicine and Biology, Vol. 39, No. 5, 01.07.2012, p. 715-723.

Research output: Contribution to journalArticle

Tarkia, M, Saraste, A, Saanijoki, T, Oikonen, V, Vähäsilta, T, Strandberg, M, Stark, C, Tolvanen, T, Teräs, M, Savunen, T, Green, MA, Knuuti, J & Roivainen, A 2012, 'Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs', Nuclear Medicine and Biology, vol. 39, no. 5, pp. 715-723. https://doi.org/10.1016/j.nucmedbio.2011.11.007
Tarkia M, Saraste A, Saanijoki T, Oikonen V, Vähäsilta T, Strandberg M et al. Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs. Nuclear Medicine and Biology. 2012 Jul 1;39(5):715-723. https://doi.org/10.1016/j.nucmedbio.2011.11.007
Tarkia, Miikka ; Saraste, Antti ; Saanijoki, Tiina ; Oikonen, Vesa ; Vähäsilta, Tommi ; Strandberg, Marjatta ; Stark, Christoffer ; Tolvanen, Tuula ; Teräs, Mika ; Savunen, Timo ; Green, Mark A. ; Knuuti, Juhani ; Roivainen, Anne. / Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs. In: Nuclear Medicine and Biology. 2012 ; Vol. 39, No. 5. pp. 715-723.
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abstract = "Purpose: We evaluated four potential gallium-68 ( 68Ga)-labeled tracers for positron emission tomography (PET) imaging of myocardial perfusion in comparison with oxygen-15-labeled water ([ 15O]water) in healthy pigs. Four hexadentate salicylaldimine ligands derived from bis(3-aminopropyl)ethylenediamine (BAPEN) that showed promise in previous rat experiments were selected for this study. Methods: Following an evaluation of myocardial blood flow with [ 15O]water PET, the pigs (total n=14) underwent a dynamic 90-min PET study with one of four 68Ga-labeled BAPEN derivatives (n=3-5 per tracer) either at rest or under adenosine stress. Serial arterial blood samples were collected during the imaging for the measurements of total radioactivity, radiometabolites, plasma protein binding and blood-to-plasma ratio for the 68Ga chelates. Time-activity curves of the left ventricular blood pool and myocardium were derived from PET images, and metabolite-corrected arterial input function was used for kinetic modeling. Also, ex vivo biodistribution of 68Ga radioactivity was analyzed. Results: All four 68Ga tracers showed undesirably slow myocardial accumulation over time, but their in vivo stability, clearance from blood and the kinetics of the myocardium uptake varied. [ 68Ga][Ga-(sal) 2BAPDMEN] 1+ showed the highest myocardial uptake in PET images and tissue samples (myocardium-to-blood ratio 7.63±1.89, myocardium-to-lung ratio 3.03±0.33 and myocardium-to-liver ratio 1.80±0.82). However, there was no correlation between the myocardial perfusion measured with [ 15O]water and the net uptake rates or K 1 values of the 68Ga chelates. Conclusion: Our results revealed that myocardial accumulation of the 68Ga chelates proposed for myocardial perfusion imaging with PET was slow and not determined by myocardial perfusion in a large animal model. These findings suggest that the studied tracers are not suitable for clinical imaging of myocardial perfusion.",
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AU - Saraste, Antti

AU - Saanijoki, Tiina

AU - Oikonen, Vesa

AU - Vähäsilta, Tommi

AU - Strandberg, Marjatta

AU - Stark, Christoffer

AU - Tolvanen, Tuula

AU - Teräs, Mika

AU - Savunen, Timo

AU - Green, Mark A.

AU - Knuuti, Juhani

AU - Roivainen, Anne

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N2 - Purpose: We evaluated four potential gallium-68 ( 68Ga)-labeled tracers for positron emission tomography (PET) imaging of myocardial perfusion in comparison with oxygen-15-labeled water ([ 15O]water) in healthy pigs. Four hexadentate salicylaldimine ligands derived from bis(3-aminopropyl)ethylenediamine (BAPEN) that showed promise in previous rat experiments were selected for this study. Methods: Following an evaluation of myocardial blood flow with [ 15O]water PET, the pigs (total n=14) underwent a dynamic 90-min PET study with one of four 68Ga-labeled BAPEN derivatives (n=3-5 per tracer) either at rest or under adenosine stress. Serial arterial blood samples were collected during the imaging for the measurements of total radioactivity, radiometabolites, plasma protein binding and blood-to-plasma ratio for the 68Ga chelates. Time-activity curves of the left ventricular blood pool and myocardium were derived from PET images, and metabolite-corrected arterial input function was used for kinetic modeling. Also, ex vivo biodistribution of 68Ga radioactivity was analyzed. Results: All four 68Ga tracers showed undesirably slow myocardial accumulation over time, but their in vivo stability, clearance from blood and the kinetics of the myocardium uptake varied. [ 68Ga][Ga-(sal) 2BAPDMEN] 1+ showed the highest myocardial uptake in PET images and tissue samples (myocardium-to-blood ratio 7.63±1.89, myocardium-to-lung ratio 3.03±0.33 and myocardium-to-liver ratio 1.80±0.82). However, there was no correlation between the myocardial perfusion measured with [ 15O]water and the net uptake rates or K 1 values of the 68Ga chelates. Conclusion: Our results revealed that myocardial accumulation of the 68Ga chelates proposed for myocardial perfusion imaging with PET was slow and not determined by myocardial perfusion in a large animal model. These findings suggest that the studied tracers are not suitable for clinical imaging of myocardial perfusion.

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KW - Gallium-68

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