Effect of albumin fusion on the biodistribution of interleukin-2
Effect of albumin fusion on the biodistribution of interleukin-2
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DOI：
10.1007/s00262-003-0454-z
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发表时间：
2004-05-01
影响因子：
5.8
通讯作者：
Sung, C
中科院分区：
文献类型：
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作者：
Yao, ZS;Dai, WL;Sung, C
目的研究人血清白蛋白（HSA）-白细胞介素-2（IL-2）融合蛋白白细胞介素（Albuleukin）在小鼠体内的分布，IL-2和HSA的水平。目的是确定白介素是否由于其与HSA的基因融合而与IL-2不同地分布于正常器官和淋巴组织。（13-异硫氰酸根合苄基）-环己基-二亚乙基三胺五乙酸（选择CHX-A（II）用于In-111放射性标记，与CHX-A（II）偶联后，IL-2和白细胞介素对CTLL-2细胞增殖的生物活性无明显改变。将放射性标记的蛋白质静脉注射到小鼠体内，测量器官中的摄取，并进行全身放射自显影术。In-111-IL-2从血液中迅速清除，在注射后20分钟时小于1% ID/g（每克组织注射剂量的百分比）。此时，肾脏显示超过120% ID/g摄取，并且这些高水平持续6 h。相比之下，In-111-白蛋白显示出显著更长的循环（6小时14%ID/g），更低的肾脏摄取（
Purpose We investigated and compared the biodistribution of Albuleukin, a human serum albumin (HSA)-interleukin-2 (IL-2) fusion protein., with those of IL-2 and HSA. The objective was to determine whether Albuleukin distributes differently to normal organs and lymphoid tissues than IL-2 by virtue of its genetic fusion with HSA.Methods The chelating agent 2-(13-isothiocyanatobenzyl)-cyclohexyl-diethylenetriaminepentaacetic acid (CHX-A(II) was selected for radiolabeling with In-111, and conjugation with CHX-A(II) did not alter bioactivities of IL-2 and Albuleukin on proliferation of CTLL-2 cells. The radiolabeled proteins were injected intravenously into mice, uptake in organs was measured, and whole-body autoradiography was performed.Results Striking differences in the biodistribution of IL-2 and Albuleukin were noted. In-111-IL-2 cleared from blood rapidly, with less than 1% ID/g (percentage of injected dose per gram of tissue) at 20 min after injection. At this time, the kidneys showed more than 120% ID/g uptake, and these high levels persisted through 6 h. In-111-Albuleukin, by contrast, showed significantly longer circulation (14% ID/g at 6 h), lower kidney uptake (