Miller D D, Boulet A J, Tio F O, Garcia O J, Guy D M, McEver R P, Palmaz J C, Pak K Y, Neblock D S, Berger H J
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7872.
Circulation. 1991 Jan;83(1):224-36. doi: 10.1161/01.cir.83.1.224.
To examine the specificity of technetium-99m monoclonal antibody (S12) imaging for identifying activated platelets at interventional injury sites in atherosclerotic rabbit arteries, subgroups of unheparinized rabbits (n = 39) underwent serial percutaneous transluminal aortic angioplasty (PTA) procedures (with or without intravascular stent placement) followed by in vivo and then ex vivo gamma camera imaging, scanning, and immunoelectron microscopy to determine the intravascular loci of S12 Fab' antibody binding. Despite angiographic vessel patency, image-derived ratios of in vivo S12 binding in injured versus uninjured vascular segments were significantly increased (p less than 0.05) after one PTA (1.3 +/- 0.17, n = 7), PTA twice at 6-week intervals (1.4 +/- 0.22, n = 7), and PTA plus stent placement (1.6 +/- 0.28, n = 7) compared with control experiments (1.1 +/- 0.13, n = 7). Ex vivo imaging of blood-free excised aortas confirmed S12 localization at PTA (2 +/- 0.4, n = 3) and PTA plus stent placement (5 +/- 3.8, n = 7) sites (both p less than 0.05 versus controls). S12 antibody uptake decreased significantly (p less than 0.05) at 1 week after PTA plus stent placement in vivo (1.1 +/- 0.10, n = 4) and ex vivo (1.6 +/- 0.7, n = 3). Electron microscopic studies confirmed dense platelet, fibrin, and red blood cell deposition in regions of acute injury, with endothelial neointimal proliferation at 1 week after PTA. Immunoelectron microscopic studies confirmed specific in vivo S12 binding (22:1 versus nonrelevant IgG) at sites of alpha-granule GMP-140 expression in activated platelets. Therefore, S12 studies may be useful to localize sites of platelet-derived mitogen release at arterial PTA injury sites.
为了研究锝-99m单克隆抗体(S12)成像在识别动脉粥样硬化兔动脉介入损伤部位活化血小板方面的特异性,未使用肝素的兔亚组(n = 39)接受了系列经皮腔内血管成形术(PTA)操作(有或无血管内支架置入),随后进行体内和体外γ相机成像、扫描以及免疫电子显微镜检查,以确定S12 Fab'抗体结合的血管内位点。尽管血管造影显示血管通畅,但在进行一次PTA(1.3±0.17,n = 7)、每6周进行两次PTA(1.4±0.22,n = 7)以及PTA加支架置入(1.6±0.28,n = 7)后,与对照实验(1.1±0.13,n = 7)相比,损伤血管段与未损伤血管段的体内S12结合的图像衍生比值显著增加(p<0.05)。对无血切除主动脉的体外成像证实S12定位于PTA(2±0.4,n = 3)和PTA加支架置入(5±3.8,n = 7)部位(与对照组相比,两者p均<0.05)。在体内(1.1±0.10,n = 4)和体外(1.6±0.7,n = 3)进行PTA加支架置入后1周,S12抗体摄取显著降低(p<0.05)。电子显微镜研究证实急性损伤区域有密集的血小板、纤维蛋白和红细胞沉积,PTA后1周有内皮新生内膜增殖。免疫电子显微镜研究证实在活化血小板中α颗粒GMP-140表达部位存在特异性的体内S12结合(22:1相对于无关IgG)。因此,S12研究可能有助于定位动脉PTA损伤部位血小板衍生促有丝分裂原释放的位点。