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

PurposeWe 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.MethodsFollowing 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.ResultsAll 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.ConclusionOur 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.