Layne W W, Hnatowich D J, Doherty P W, Childs R L, Lanteigne D, Ansell J
J Nucl Med. 1982 Jul;23(7):627-30.
In earlier work, DTPA has been covalently coupled to albumin via the cyclic anhydride of DTPA. Using fibrinogen, we have studied the effect of such coupling on protein viability by both an in vitro and an in vivo assay. Clotting time remained identical to that of the native protein whether the anhydride-to-protein molar ratio was 1:1 or 5:1. In vivo studies were done in dogs, with human fibrinogen labeled with 1-125 and In-111. Throughout 130 hr, blood clearances for the two tracers agreed whether with 1:1 or 5:1 coupling. In a dog model with a thrombogenic catheter, the clot-to-blood ratios for the two radiotracers agreed within experimental error. Finally, 1:1-coupled canine fibrinogen, labeled with In-111, was administered to dogs with a catheter in a jugular vein, and scintigrams at 24 hr clearly showed clotting along the length of the catheter. We conclude that fibrinogen, coupled to DTPA, retains its viability, behaving like radioiodinated fibrinogen in vivo, and In-111 labeled fibrinogen looks promising as a clinical diagnostic agent.
在早期的研究工作中，二乙三胺五乙酸（DTPA）已通过其环状酸酐与白蛋白共价偶联。利用纤维蛋白原，我们通过体外和体内试验研究了这种偶联对蛋白质活性的影响。无论酸酐与蛋白质的摩尔比是1:1还是5:1，凝血时间都与天然蛋白质的凝血时间相同。体内研究在狗身上进行，使用用碘-125和铟-111标记的人纤维蛋白原。在整个130小时内，两种示踪剂的血液清除率在1:1或5:1偶联时是一致的。在一个带有致血栓形成导管的狗模型中，两种放射性示踪剂的凝块与血液的比率在实验误差范围内是一致的。最后，将用铟-111标记的1:1偶联犬纤维蛋白原注入颈静脉置有导管的狗体内，24小时的闪烁扫描图清楚地显示了沿导管长度的凝血情况。我们得出结论，与DTPA偶联的纤维蛋白原保留了其活性，在体内的行为类似于放射性碘化纤维蛋白原，并且铟-111标记的纤维蛋白原作为一种临床诊断剂看起来很有前景。
