Radiogallium localization in tumors: blood binding and transport and the role of transferrin.
Radiogallium localization in tumors: blood binding and transport and the role of transferrin.
复制标题
放射性镓在肿瘤中的定位：血液结合和运输以及转铁蛋白的作用。
作者：
S. Vallabhajosula;J. Harwig;J. Siemsen;W. Wolf
作为了解镓在肿瘤定位的关键一步，我们重新研究了镓在血液中的结合和运输。在兔体内注射枸橼酸镓67，在体外与单个血浆蛋白孵育。通过超滤和凝胶过滤层析，兔血浆样品显示基本完全的蛋白质结合，而透析显示相当多的非蛋白质结合镓，其数量取决于透析介质。电泳结果显示，总结合量与电泳时间成反比。亲和层析显示，所有的镓都与转铁蛋白结合，而电泳则导致镓与转铁蛋白持续分离，并在其他各种蛋白质带上出现未结合的放射性。同样，在体外培养研究中，镓与转铁蛋白的结合与电泳时间成反比，而超滤和凝胶过滤色谱显示所有镓都与转铁蛋白结合。没有观察到镓与其他蛋白质（如白蛋白）的结合。该研究表明，血液中示踪剂水平的镓完全与转铁蛋白结合并通过转铁蛋白运输，并表明易解离的金属配合物的电泳和透析受到明显的伪影影响。准确测定放射性药物的蛋白质结合需要结合分析技术和对结果的谨慎解释。«少
As a crucial step toward the understanding of the tumor localization of gallium, we have re-investigated its binding and transport in blood. The studies were performed in vivo by injection of gallium-67 citrate in rabbits, and in vitro by incubation of gallium-67 citrate with individual plasma proteins. By ultrafiltration and gel filtration chromatography, rabbit plasma samples showed essentially complete protein binding, whereas dialysis indicated considerable nonprotein-bound gallium, the amount depending on the dialysis medium. According to electrophoresis, total binding was inversely proportional to electrophoresis time. Affinity chromatography showed all gallium to be bound to transferrin, whereas electrophoresis caused continuous dissociation of gallium from transferrin, with the resulting unbound radioactivity appearing in various other protein bands. Similarly, the binding of gallium to transferrin in the in vitro incubation studies was inversely proportional to electrophoresis time, whereas ultrafiltration and gel filtration chromatography showed all gallium to be transferrin-bound. No binding of gallium to other proteins, such as albumin, was observed. This study demonstrates that gallium at the tracer level in blood is exclusively bound to and transported by transferrin, and indicates that electrophoresis and dialysis of easily dissociable metal complexes are subject to significant artifacts. Accurate determination of protein binding of radiopharmaceuticalsmore » requires a combination of analytical techniques and cautious interpretation of the results.« less