Lewis Jason S, Herrero Pilar, Sharp Terry L, Engelbach John A, Fujibayashi Yasuhisa, Laforest Richard, Kovacs Attila, Gropler Robert J, Welch Michael J
Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Nucl Med. 2002 Nov;43(11):1557-69.
Copper(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) (copper-ATSM) is a hypoxia-avid tracer for the selective identification of hypoxic tissue. Using canine models of hypoxic myocardium, we report our findings on *Cu-ATSM PET (*Cu is defined as either (60)Cu, (61)Cu, or (64)Cu) for the delineation of ischemic and hypoxic myocardium.
In protocol I, myocardial hypoxia was induced by global hypoxia (n = 3). In protocol II, myocardial ischemia was generated by occlusion of the left anterior descending coronary artery (n = 9). In protocol III, coronary artery stenosis was induced by a stenosis in the left anterior descending coronary artery (n = 4). PET dynamic data were acquired immediately after tracer injection. Tracer retention kinetics were analyzed using either monoexponential analysis (1/k(mono)) or a simple 2-compartment model (1/k(4)).
In protocol I, tracer retention in hypoxic myocardium was 2-fold greater than in normal myocardium, despite a 7-fold increase in blood flow (normal, 0.70 +/- 0.42 mL.min(-1).g(-1); hypoxic, 4.94 +/- 3.00 mL.min(-1).g(-1) [P < 0.005]). In protocol II, approximately 3 h after occlusion, retention of *Cu-ATSM within 20 min was greater in ischemic regions (myocardial blood flow, 0.28 +/- 0.26 mL.min(-1).g(-1)) than in normal tissue (myocardial blood flow, 0.52 +/- 0.19 mL.min(-1).g(-1)) (1/k(mono), 40.72 +/- 39.0 min vs. 26.69 +/- 22.29 min [P < 0.05]; 1/k(4), 6.85 +/- 4.90 min vs. 3.51 +/- 1.97 min [P < 0.05]). In selected dogs, tracer retention decreased at 24 h, suggesting the development of necrosis with no subsequent retention of *Cu-ATSM. In protocol III, dobutamine infusion after stenosis placement resulted in increased tracer retention consistent with hypoxia in the damaged regions.
*Cu-ATSM PET has shown quantitative selective uptake in hypoxic myocardium within 20 min of tracer administration in 3 canine models of hypoxia.
铜（II）-双乙酰双（N（4）-甲基硫代半卡巴腙）（铜-ATSM）是一种用于选择性识别缺氧组织的亲缺氧示踪剂。我们使用缺氧心肌的犬模型，报告了关于*铜-ATSM正电子发射断层扫描（*铜定义为（60）铜、（61）铜或（64）铜）用于描绘缺血和缺氧心肌的研究结果。
在方案I中，通过全身性缺氧诱导心肌缺氧（n = 3）。在方案II中，通过闭塞左前降支冠状动脉诱导心肌缺血（n = 9）。在方案III中，通过左前降支冠状动脉狭窄诱导冠状动脉狭窄（n = 4）。在注射示踪剂后立即采集PET动态数据。使用单指数分析（1/k（单指数））或简单的两室模型（1/k（4））分析示踪剂滞留动力学。
在方案I中，尽管血流量增加了7倍（正常，0.70±0.42 mL·min-1·g-1；缺氧，4.94±3.00 mL·min-1·g-1 [P < 0.005]），但缺氧心肌中的示踪剂滞留量比正常心肌大2倍。在方案II中，闭塞后约3小时，缺血区域（心肌血流量，0.28±0.26 mL·min-1·g-1）内铜-ATSM在20分钟内的滞留量大于正常组织（心肌血流量，0.52±0.19 mL·min-1·g-1）（1/k（单指数），40.72±39.0分钟对26.69±22.29分钟[P < 0.05]；1/k（4），6.85±4.90分钟对3.51±1.97分钟[P < 0.05]）。在选定的犬中，示踪剂滞留量在24小时时下降，表明发生坏死且随后无铜-ATSM滞留。在方案III中，放置狭窄后输注多巴酚丁胺导致示踪剂滞留增加，与受损区域的缺氧一致。
在3种犬缺氧模型中，*铜-ATSM正电子发射断层扫描在注射示踪剂后20分钟内已显示出在缺氧心肌中的定量选择性摄取。
