Molecular hybrid positron emission tomography/computed tomography imaging of cardiac angiotensin II type 1 receptors.
Molecular hybrid positron emission tomography/computed tomography imaging of cardiac angiotensin II type 1 receptors.
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DOI：
10.1016/j.jacc.2012.09.023
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发表时间：
2012-12-18
影响因子：
24
通讯作者：
Bengel, Frank M.
中科院分区：
文献类型：
--
作者：
Fukushima, Kenji;Bravo, Paco E.;Higuchi, Takahiro;Schuleri, Karl H.;Lin, Xiaoping;Abraham, M. Roselle;Xia, Jinsong;Mathews, William B.;Dannals, Robert F.;Lardo, Albert C.;Szabo, Zsolt;Bengel, Frank M.
关键词：
目的探讨应用临床正电子发射断层扫描/计算机断层扫描（PET/CT）靶向显像心脏组织血管紧张素II 1型受体（AT 1 R）的可行性。AT 1 R是一个有吸引力的成像目标，由于其在各种心脏病理，包括梗死后左心室重塑的关键作用。使用新型AT 1 R配体[11 C]-KR 31173，在健康条件下（n=4）和实验性心肌梗死后3-4周（n=5）对年轻农场猪进行动态PET/CT。通过免疫组织化学和PCR进行离体验证。在4名健康志愿者中进行了首次人体应用，在基线和AT 1 R阻断下。在健康猪中，心肌KR 31173保留是可检测的，区域均匀，特异性AT 1 R，通过阻断实验证实。血浆中的代谢较低（60 min后为完整示踪剂的85±2%）。心肌梗死后，经局部灌注校正的KR 31173保留显示梗死区相对于远端心肌的AT 1 R上调，而与健康对照组心肌相比，两个区域的保留均升高（梗死和远端vs健康对照组分别为8.7±0.8和7.1±0.3 vs 5.8± 0.4%/min; p<0.01）。尸检分析证实了AT 1 R在远端和梗死组织中的上调。首次人体应用是安全的，并显示可检测和特异性心肌KR 31173保留，尽管水平低于猪（LV平均保留：1.2±0.1 vs 4.4±1.2%/min，人vs猪; p=0.04）。应用临床PET/CT技术对心脏AT 1 R表达进行无创成像是可行的。结果为更广泛的AT 1 R靶向分子成像临床试验提供了依据。
To explore the feasibility of targeted imaging of the angiotensin II subtype 1 receptor (AT1R) in cardiac tissue, using clinical hybrid positron emission tomography/computed tomography (PET/CT). AT1R is an attractive imaging target due to its key role in various cardiac pathologies, including post-infarct left ventricular remodeling. Using the novel AT1R ligand [11C]-KR31173, dynamic PET/CT was performed in young farm pigs under healthy conditions (n=4), and 3–4 weeks after experimental myocardial infarction (n=5). Ex vivo validation was carried out by immunohistochemistry and PCR. First-in-man application was performed in 4 healthy volunteers, at baseline and under AT1R blocking. In healthy pigs, myocardial KR31173 retention was detectable, regionally homogeneous, and specific for AT1R, as confirmed by blocking experiments. Metabolism in plasma was low (85±2% of intact tracer after 60min). After myocardial infarction, KR31173 retention, corrected for regional perfusion, revealed AT1R upregulation in the infarct area relative to remote myocardium, while retention was elevated in both regions when compared to myocardium of healthy controls (8.7±0.8 and 7.1±0.3 vs 5.8±0.4 %/min for infarct and remote vs healthy controls; p<0.01 each). Postmortem analysis confirmed AT1R upregulation in remote and infarct tissue. First-in-man application was safe, and showed detectable and specific myocardial KR31173 retention, at an albeit lower level than pigs (LV average retention: 1.2±0.1 vs 4.4±1.2%/min for humans vs pigs; p=0.04). Noninvasive imaging of cardiac AT1R expression is feasible using clinical PET/CT technology. Results provide a rationale for broader clinical testing of AT1R-targeted molecular imaging.
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影响因子：
3.1
作者：
Mathews, WB;Yoo, SE;Szabo, Z
通讯作者：
Szabo, Z
影响因子：
5.7
作者：
Heerdt, PM;Gandhi, CD;Dickstein, ML
通讯作者：
Dickstein, ML
影响因子：
9.3
作者：
Holz, Andrew;Lautamaeki, Riikka;Bengel, Frank M.
通讯作者：
Bengel, Frank M.
影响因子：
14
作者：
Verjans, Johan W. H.;Lovhaug, Dagfinn;Narula, Jagat
通讯作者：
Narula, Jagat
DOI：
10.1007/s00259-007-0607-y
发表时间：
2008-02-01
影响因子：
9.1
作者：
Lautamaeki, Riikka;Brown, Tracy L. Y.;Bengel, Frank M.
通讯作者：
Bengel, Frank M.