title: Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs.
abstract: OBJECTIVE
  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 K1 values of the 68Ga chelates.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Turku PET Centre, Department of Medicine, University of Turku and Turku University Hospital, FI-20521 Turku, Finland. miikka.tarkia@tyks.fi
authors.forename: Miikka
authors.initials: M
authors.lastname: Tarkia
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.forename: Tiina
authors.initials: T
authors.lastname: Saanijoki
authors.forename: Vesa
authors.initials: V
authors.lastname: Oikonen
authors.forename: Tommi
authors.initials: T
authors.lastname: Vähäsilta
authors.forename: Marjatta
authors.initials: M
authors.lastname: Strandberg
authors.forename: Christoffer
authors.initials: C
authors.lastname: Stark
authors.forename: Tuula
authors.initials: T
authors.lastname: Tolvanen
authors.forename: Mika
authors.initials: M
authors.lastname: Teräs
authors.forename: Timo
authors.initials: T
authors.lastname: Savunen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Green
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
mesh_terms: D000818:Animals; D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism; D005029:Ethylenediamines / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D005710:Gallium Radioisotopes; D008024:Ligands; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D009206:Myocardium / Q000378:metabolism; D009942:Organometallic Compounds / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D013552:Swine
chemical_list: D001798:Blood Proteins; D005029:Ethylenediamines; D005710:Gallium Radioisotopes; D008024:Ligands; D009942:Organometallic Compounds; D011849:Radioactive Tracers; C081867:gallium bis(4,6-dimethoxy)salicylaldimine N,N'-bis(3-aminopropyl)ethylenediamine