Stable Delineation of the Ischemic Area by the PET Perfusion Tracer 18F-Fluorobenzyl Triphenyl Phosphonium After Transient Coronary Occlusion
Stable Delineation of the Ischemic Area by the PET Perfusion Tracer 18F-Fluorobenzyl Triphenyl Phosphonium After Transient Coronary Occlusion
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DOI：
10.2967/jnumed.110.085993
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发表时间：
2011-06-01
影响因子：
9.3
通讯作者：
Bengel, Frank M.
中科院分区：
文献类型：
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作者：
Higuchi, Takahiro;Fukushima, Kenji;Bengel, Frank M.
F-18-氟苄基三苯基膦（FBnTP）最近被引入作为心肌灌注PET剂。我们使用大鼠短暂冠状动脉闭塞模型来确定灌注缺损大小随时间的稳定性和再分布的幅度。方法：Wistar大鼠（n = 15）行开胸左冠状动脉（LCA）阻断2分钟，然后再灌注。在闭塞期间，静脉内注射F-18-FBnTP（92.5 MBq）和Tl-201-氯化铊（0.74 MBq）。再灌注后5、45和120 min处死动物，于再灌注前1 min再次阻断LCA，静脉注射2%伊文思蓝，以确定缺血区域。将心脏切除、冷冻并切片用于连续双示踪剂放射自显影和组织学检查。对动物亚组（n = 4）进行动态体内F-18-FBnTP PET。结果：F-18-FBnTP在示踪剂注射和再灌注后的所有时间点均显示稳定的缺血缺损。缺陷匹配蓝色染料缺陷（y = 0.97x +1.5，R-2 = 0.94，y =蓝色染料缺陷，x = F-18-FBnTP缺陷）。计数密度分析显示，在45分钟时没有缺损填充，但在120分钟时活性略有增加（在5、45和120分钟时LCA/远端摄取比分别= 0.19 +/- 0.02、0.19 +/- 0.05和0.34 +/- 0.06，P < 0.05）。为了比较，T1 -201在120分钟时显示完全再分布（在5、45和120分钟时LCA/远程分别= 0.42 +/- 0.04、0.72 +/- 0.03和0.97 +/- 0.05，P < 0.001）。通过体内动态小动物PET证实了F-18-FBnTP缺陷随时间的持续性。结论：在短暂性冠状动脉闭塞模型中，使用新PET剂F-18-FBnTP的灌注缺损大小保持稳定至少45分钟，并与组织学定义的缺血区域相匹配。这种缺乏显著的再分布表明，未来的临床协议有足够的时间窗口，示踪剂注射远离扫描仪，如在压力测试实验室或胸痛单位。
F-18-fluorobenzyl triphenyl phosphonium (FBnTP) has recently been introduced as a myocardial perfusion PET agent. We used a rat model of transient coronary occlusion to determine the stability of the perfusion defect size over time and the magnitude of redistribution. Methods: Wistar rats (n = 15) underwent thoracotomy and 2-min occlusion of the left coronary artery (LCA), followed by reperfusion. During occlusion, F-18-FBnTP (92.5 MBq) and Tl-201-thallium chloride (0.74 MBq) were injected intravenously. One minute before the animals were sacrificed at 5, 45, and 120 min after reperfusion, the LCA was occluded again and 2% Evans blue was injected intravenously to determine the ischemic territory. The hearts were excised, frozen, and sliced for serial dual-tracer autoradiography and histology. Dynamic in vivo F-18-FBnTP PET was performed on a subgroup of animals (n = 4). Results: F-18-FBnTP showed stable ischemic defects at all time points after tracer injection and reperfusion. The defects matched the blue dye defect (y = 0.97x +1.5, R-2 = 0.94, y = blue-dye defect, x = F-18-FBnTP defect). Count density analysis showed no defect fill-in at 45 min but slightly increased activity at 120 min (LCA/remote uptake ratio = 0.19 +/- 0.02, 0.19 +/- 0.05, and 0.34 +/- 0.06 at 5, 45, and 120 min, respectively, P < 0.05). For comparison, Tl-201 showed complete redistribution at 120 min (LCA/remote = 0.42 +/- 0.04, 0.72 +/- 0.03, and 0.97 +/- 0.05 at 5, 45, and 120 min, respectively, P < 0.001). Persistence of the F-18-FBnTP defect over time was confirmed by in vivo dynamic small-animal PET. Conclusion: In a transient coronary occlusion model, perfusion defect size using the new PET agent F-18-FBnTP remained stable for at least 45 min and matched the histologically defined ischemic area. This lack of significant redistribution suggests a sufficient time window for future clinical protocols with tracer injection remote from the scanner, such as in a stress testing laboratory or chest pain unit.