Fischman A J, Rubin R H, White J A, Locke E, Wilkinson R A, Nedelman M, Callahan R J, Khaw B A, Strauss H W
Department of Radiology, Massachusetts General Hospital, Boston 02114.
J Nucl Med. 1990 Jul;31(7):1199-205.
Intact IgG, Fc, Fab, and 1/2Fc (reduced and alkylated Fc) were coupled to DTPA, labeled with indium-111 and administered to rats to compare the ability of fragments of IgG to localize at focal sites of inflammation. Two sets of experiments were performed: First, 1, 6, 24, and 48 hr after injection, biodistribution was determined in healthy animals; second, localization at sites of inflammation was determined by scintillation camera imaging of animals with deep-thigh infection due to Escherichia coli. The biodistribution studies demonstrated differences in kidney and liver localization: IgG less than Fc less than Fab less than 1/2Fc (kidney), Fc less than 1/2Fc less than IgG less than Fab (liver). The imaging studies revealed that target-to-background ratio (T/B) and percent residual activity (%RA) for IgG was significantly greater (p less than 0.01) than 1/2 Fc or Fab, and T/B for IgG was greater (p less than 0.01) than Fc. These studies suggest that the Fc portion of IgG is the fragment with the best imaging properties.
完整的IgG、Fc、Fab和1/2Fc(还原和烷基化的Fc)与二乙三胺五乙酸(DTPA)偶联,用铟-111标记后给大鼠注射,以比较IgG片段在炎症灶部位的定位能力。进行了两组实验:第一,在注射后1、6、24和48小时,测定健康动物体内的生物分布;第二,通过闪烁相机对因大肠杆菌引起大腿深部感染的动物进行成像,确定炎症部位的定位情况。生物分布研究表明,在肾脏和肝脏定位方面存在差异:IgG<Fc<Fab<1/2Fc(肾脏),Fc<1/2Fc<IgG<Fab(肝脏)。成像研究显示,IgG的靶本比(T/B)和残留活性百分比(%RA)显著高于1/2Fc或Fab(p<0.01),且IgG的T/B高于Fc(p<0.01)。这些研究表明,IgG的Fc部分是具有最佳成像特性的片段。