Radiolabeled Arginine-Glycine-Aspartic Acid Peptides to Image Angiogenesis in Swine Model of Hibernating Myocardium
Radiolabeled Arginine-Glycine-Aspartic Acid Peptides to Image Angiogenesis in Swine Model of Hibernating Myocardium
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DOI：
10.1016/j.jcmg.2008.05.002
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发表时间：
2008-07-01
影响因子：
14
通讯作者：
Haubner, Roland
中科院分区：
文献类型：
--
作者：
Johnson, Lynne L.;Schofield, Lorraine;Haubner, Roland
目的应用靶向α-v-β3整合素的[I-123]葡萄糖-精氨酸-甘氨酸-天冬氨酸(RGD)对猪冬眠心肌模型心肌内注射phVEGF(165)所产生的血管生成进行成像。细胞外基质与血管内皮细胞之间的相互作用主要受通过RGD基序结合的αvβ3整合素的影响。方法在21+/-4天，8只猪在非透视三维心内膜标测系统(NOGA)引导下，分6个部位心内膜心肌注射1.2 mg phVEGF165，6只猪注射生理盐水(S)。20+/-6d后，13只动物注射6.4+/-1.7MCI[I-123]GLuco-RGD，1只注射血管内皮生长因子(VEGF)的I-123标记肽对照，所有动物注射2.5+/-0.4MCI的TI-201并进行单光子发射计算机断层扫描。在两个时间点进行血流和超声心动图测量，并通过凝集素染色分析组织纤维化和毛细血管密度。结果与远程相比，注射时非晶状体缩窄区冬眠心肌的室壁增厚减少。血管内皮细胞生长因子组左回旋支/左前降支心肌血流量比值增加15+/-11%，注射S组降低13+/-12%(P<；0.01)。血管内皮细胞生长因子治疗后缩窄区的管壁增厚略有增加(8+/-17%)，而注射S的动物管壁增厚减少23+/-31%(P=0.01vs血管内皮细胞生长因子)。血管内皮生长因子注射组的凝集素染色阳性组织百分率高于S注射组(2.5+/-1.5%vs.0.87+/-0.52%，P=0.01)。注射血管内皮生长因子的动物可见与TI-201缺陷相对应的[I-123]葡萄糖-RGD的局部摄取，而注射S的动物则未见此现象。结论放射性标记的RGD多肽的单光子发射计算机断层扫描成像可能是监测心脏血管生成治疗的一种有用的非侵入性方法。(J Am Coll Hearol IMG 2008；1：500-10)(C)2008，美国心脏病学会基金会
OBJECTIVES Our aim was to image angiogenesis produced by endomyocardial injection of phVEGF(165) in a swine model of hibernating myocardium using [I-123] Gluco-arginine-glycine-aspartic acid (RGD) targeting the alpha v beta 3 integrins.BACKGROUND A noninvasive test to monitor the efficacy of therapy inducing angiogenesis is needed. The interaction between extracellular matrix and endothelial cells in sprouting capillaries is effected primarily by alpha v beta 3 integrins that bind through RGD motifs.METHODS At 21 +/- 4 days, after left circumflex coronary artery ameroid constrictor placement, 8 swine received endomyocardial injection of 1.2 mg phVEGF(165) divided into 6 sites and 6 swine received saline (S) using nonfluoroscopic 3-dimensional endocardial mapping system (Noga)-guided delivery. After 20 +/- 6 days, 13 animals were injected with 6.4 +/- 1.7 mCi [I-123]Gluco-RGD, 1 VEGF (vascular endothelial growth factor)-injected animal with I-123-labeled peptide control, and all animals with 2.5 +/- 0.4 mCi of TI-201 and underwent single-photon emission computed tomography imaging. Blood flow and echocardiographic measurements were made at both time points and tissue analyzed for fibrosis and capillary density by lectin staining.RESULTS Hibernating myocardium in the ameroid constrictor territory at time of injections was documented by reduced wall thickening compared with remote. Ratio of myocardial blood flow in left circumflex coronary artery/left anterior descending coronary artery territories increased by 15 +/- 11% in the VEGF animals and fell 13 +/- 12% in S-injected (p < 0.01). There was a small increase in wall thickening in constrictor territory after VEGF (8 +/- 17%) while in S-injected animals wall thickening fell by 23 +/- 31% (p = 0.01 vs. VEGF). Lectin staining as percent positive tissue staining for ameroid territory was higher in VEGF-injected compared with S-injected animals (2.5 +/- 1.5% vs. 0.87 +/- 0.52%, p = 0.01). Focal uptake of [I-123] Gluco-RGD corresponding to TI-201 defects was seen in VEGF-injected but not in S-injected animals. [I-123] Gluco-RGD uptake in the ameroid territory as percent injected dose correlated with lectin staining (R-2 = 0.80, p = 0.002).CONCLUSIONS These data suggest that single-photon emission computed tomography imaging of radiolabeled RGD peptides may be a useful noninvasive method to monitor therapy that induces angiogenesis in the heart. (J Am Coll Cardiol Img 2008; 1:500-10) (C) 2008 by the American College of Cardiology Foundation