Division of Nuclear Medicine, Russell H Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland, USA.
J Nucl Med. 2011 Jun;52(6):965-9. doi: 10.2967/jnumed.110.085993. Epub 2011 May 13.
(18)F-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.
Wistar rats (n = 15) underwent thoracotomy and 2-min occlusion of the left coronary artery (LCA), followed by reperfusion. During occlusion, (18)F-FBnTP (92.5 MBq) and (201)Tl-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 (18)F-FBnTP PET was performed on a subgroup of animals (n = 4).
(18)F-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 = (18)F-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, (201)Tl 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 (18)F-FBnTP defect over time was confirmed by in vivo dynamic small-animal PET.
In a transient coronary occlusion model, perfusion defect size using the new PET agent (18)F-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.
(18)F-氟苄基三苯基膦(FBnTP)最近被引入作为心肌灌注 PET 造影剂。我们使用大鼠短暂性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程度。
Wistar 大鼠(n=15)行开胸术,左冠状动脉(LCA)闭塞 2 分钟,然后再灌注。在闭塞期间,静脉注射(18)F-FBnTP(92.5MBq)和(201)Tl-氯化铊(0.74MBq)。再灌注后 5、45 和 120 分钟处死动物前 1 分钟,再次闭塞 LCA,并静脉注射 2% Evans 蓝以确定缺血区。取出心脏,冷冻,切片进行连续双示踪剂放射自显影和组织学检查。对一部分动物(n=4)进行了(18)F-FBnTP 的动态体内 PET 检查。
在再灌注后的所有时间点,(18)F-FBnTP 均显示稳定的缺血性缺损。缺陷与蓝色染料缺陷相匹配(y=0.97x+1.5,R(2)=0.94,y=蓝色染料缺陷,x=(18)F-FBnTP 缺陷)。计数密度分析显示,45 分钟时无缺损填充,但 120 分钟时活性略有增加(5、45 和 120 分钟时 LCA/远侧摄取比值分别为 0.19±0.02、0.19±0.05 和 0.34±0.06,P<0.05)。相比之下,(201)Tl 在 120 分钟时完全再分布(5、45 和 120 分钟时 LCA/远侧比值分别为 0.42±0.04、0.72±0.03 和 0.97±0.05,P<0.001)。体内小动物 PET 动态检查证实,(18)F-FBnTP 灌注缺损大小在至少 45 分钟内保持稳定,与组织学定义的缺血区相匹配。这种缺乏明显再分布的现象表明,对于未来的临床方案,存在足够的时间窗口,例如在扫描仪外的应激测试实验室或胸痛单元注射示踪剂。