ten Kate C I, Fischman A J, Rubin R H, Fucello A J, Riexinger D, Wilkinson R A, Du L, Khaw B A, Strauss H W
Division of Nuclear Medicine, Massachusetts General Hospital, Boston.
Eur J Nucl Med. 1990;17(6-8):305-9. doi: 10.1007/BF01268020.
Electrostatic effects play an important role in protein interactions and may alter the biodistribution of antibodies. To study the effect of molecular charge of the biodistribution and infection imaging properties of human polyclonal immunoglobulin G (IgG), its isoelectric point was varied by changing the level of diethylene triamine penta-acetic acid (DTPA) substitution: 0.8, 0.9, 3.7, 5.1 and 5.9 DTPA/IgG. Biodistributions of the different IgG preparations were determined at 10 min, 1, 6, 24, and 48 h post injection in normal rats, and infection imaging properties were determined in rats with Escherichia coli thigh infections. The biodistribution was significantly affected by pI. The immunoglobulin preparations with 0.9 and 3.7 DTPA/IgG showed faster clearance from the circulation and generally lower accumulation in most organs. The images had a target-to-background ratio of approximately 1.3-2.3:1. These results suggest that even though targeting is not affected by the level of DTPA substitutions, preparations with 0.9 and 3.7 DTPA/IgG may be superior imaging agents because of reduced accumulation by background organs.
静电效应在蛋白质相互作用中起着重要作用，并且可能改变抗体的生物分布。为了研究分子电荷对人多克隆免疫球蛋白G（IgG）的生物分布和感染成像特性的影响，通过改变二亚乙基三胺五乙酸（DTPA）取代水平来改变其等电点：0.8、0.9、3.7、5.1和5.9 DTPA/IgG。在正常大鼠注射后10分钟、1小时、6小时、24小时和48小时测定不同IgG制剂的生物分布，并在患有大肠杆菌大腿感染的大鼠中测定感染成像特性。生物分布受等电点的显著影响。含有0.9和3.7 DTPA/IgG的免疫球蛋白制剂显示出从循环中更快的清除，并且在大多数器官中的积累通常较低。图像的靶本比约为1.3 - 2.3:1。这些结果表明，尽管靶向不受DTPA取代水平的影响，但含有0.9和3.7 DTPA/IgG的制剂可能是更优的成像剂，因为背景器官的积累减少。
