Turku PET Centre, Department of Medicine, University of Turku and Turku University Hospital, FI-20521 Turku, Finland.
Nucl Med Biol. 2012 Jul;39(5):715-23. doi: 10.1016/j.nucmedbio.2011.11.007. Epub 2012 Jan 20.
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.
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.
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.
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.
我们评估了四种潜在的镓-68（68Ga）标记示踪剂，用于与氧-15 标记水（[15O]水）比较，对健康猪的心肌灌注进行正电子发射断层扫描（PET）成像。在以前的大鼠实验中表现出前景的四种源自双（3-氨基丙基）乙二胺（BAPEN）的六齿席夫碱配体被选为本研究。
在用[15O]水 PET 评估心肌血流后，14 只猪（每组 n=3-5）进行了 90 分钟的动态 PET 研究，其中 4 只接受了一种 68Ga 标记的 BAPEN 衍生物之一的研究（n=3-5），要么在休息时，要么在腺苷应激下。在成像过程中，连续采集动脉血样，用于测量 68Ga 螯合物的总放射性、放射性代谢物、血浆蛋白结合率和血液与血浆比。从 PET 图像中得出左心室血池和心肌的时间-活性曲线，并使用代谢校正的动脉输入函数进行动力学建模。此外，还分析了 68Ga 放射性的离体生物分布。
所有四种 68Ga 示踪剂的心肌积累都随时间推移而缓慢，但其体内稳定性、血液清除率和心肌摄取动力学各不相同。[68Ga][Ga-（sal）2BAPDMEN]1+在 PET 图像和组织样本中显示出最高的心肌摄取量（心肌与血液比 7.63±1.89，心肌与肺比 3.03±0.33 和心肌与肝比 1.80±0.82）。然而，用[15O]水测量的心肌灌注与 68Ga 螯合物的净摄取率或 K1 值之间没有相关性。
我们的结果表明，在大型动物模型中，用于 PET 心肌灌注成像的 68Ga 螯合物的心肌积累缓慢，且不受心肌灌注的影响。这些发现表明，所研究的示踪剂不适合用于心肌灌注的临床成像。
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