99mTc-labeled mannosyl-neoglycoalbumin for sentinel lymph node identification
99mTc-labeled mannosyl-neoglycoalbumin for sentinel lymph node identification
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DOI：
10.1016/j.nucmedbio.2004.04.008
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发表时间：
2004-10-01
影响因子：
3.1
通讯作者：
Arano, Y
中科院分区：
文献类型：
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作者：
Takagi, K;Uehara, T;Arano, Y
由于Tc-99 m标记的人血清白蛋白（HSA）可迅速从注射部位清除，因此制备并评价了Tc-99 m标记的甘露糖基-新糖蛋白（NMA）作为前哨淋巴结（SLN）识别的放射性药物。将NMA与6-肼基吡啶-3-羧酸（HYNIC）缀合，并与[Tc-99 m]（tricine）（2）反应以制备[Tc-99 m]（HYNIC-NMA）（tricine）（2）。从小鼠足垫皮下注射[Tc-99 m]（HYNIC-NMA）（tricine）（2）后，将腘和腰淋巴结、注射部位和其他组织中的放射性水平与[Tc-99 m]（HYNIC-HSA）（tricine）（2）和Tc-99 m标记的胶体硫酸异丙酯（[Tc-99 m]胶体）的放射性水平进行比较。在注射后0.5、1和6 h，[（TC）-T-99 m]（HYNIC-NMA）（tricine）2在腘淋巴结（该模型中的SLN）中的放射性水平显著高于[Tc-99 m]（HYNIC-HSA）（tricine）（2）和[Tc-99 m]胶体。[Tc-99 m]（HYNIC-NMA）（tricine）（2）显示腘动脉蓄积呈剂量依赖性降低，而血液、肝脏和脾脏中的放射性水平随着NMA摩尔剂量的增加而增加。[Tc-99 m]胶体记录到腘淋巴结、血液、肝脏和脾脏中的放射性水平随稀释而降低。然而，注射部位的放射性水平随着[ Tc-99 m]胶体的稀释而增加。[Tc-99 m]（HYNIC-NMA）（tricine）（2）和[Tc-99 m]（HYNIC-HSA）（tricine）（2）显示注射部位的放射性水平彼此相似。这些结果表明，添加巨噬细胞结合功能的Tc-99 m标记的HSA提供了高的和选择性的放射性在SLN中的积累，而不影响从注射部位的消除速率。这些特性使得[Tc-99 m]（HYNIC-NMA）（tricine）（2）作为用于SLN鉴定的放射性药物具有吸引力。这项研究还表明，非放射性标记的胶体颗粒的数量和甘露糖基化化合物的摩尔剂量在SLN的积累中起着至关重要的作用。(C)2004年爱思唯尔公司All rights reserved.
Tc-99m-labeled mannosyl-neoglycoalbumin (NMA) was prepared and evaluated as a radiopharmaceutical for sentinel lymph node (SLN) identification, since Tc-99m-labeled human serum albumin (HSA) rapidly cleared from injection sites. NMA was conjugated with 6-hydrazinopyridine-3-carboxylic acid (HYNIC) and reacted with [Tc-99m](tricine)(2) to prepare [Tc-99m](HYNIC-NMA)(tricine)(2). After subcutaneous injection of [Tc-99m](HYNIC-NMA)(tricine)(2) from murine foot pad, radioactivity levels in the popliteal and lumbar lymph nodes, the injection site and other tissues were compared with those of [Tc-99m](HYNIC-HSA)(tricine)(2) and Tc-99m-labeled colloidal rhenium sulfate ([Tc-99m]colloid). [(TC)-T-99m](HYNIC-NMA)(tricine)2 demonstrated significantly higher radioactivity levels in the popliteal lymph node, the SLN in this model, than did [Tc-99m](HYNIC-HSA)(tricine)(2) and [Tc-99m]colloid at 0.5, 1, and 6 h post-injection. [Tc-99m](HYNIC-NMA)(tricine)(2) showed a dose-dependent decrease in the popliteal accumulation while the radioactivity levels in the blood, liver and spleen increased with an increase in the molar dose of NMA. [Tc-99m]colloid registered a decrease in the radioactivity levels in the popliteal lymph node, blood, liver, and spleen with dilution. However, the radioactivity levels at the injection site increased with dilution of [ Tc-99m] colloid. Both [Tc-99m](HYNIC-NMA)(tricine)(2) and [Tc-99m](HYNIC-HSA)(tricine)(2) showed the radioactivity levels at the injection site similar each other. These findings indicated that an addition of a macrophage binding function to Tc-99m-labeled HSA provided high and selective accumulation of the radioactivity in the SLN without affecting the elimination rate from the injection site. Such characteristics render [Tc-99m](HYNIC-NMA)(tricine)(2) attractive as a radiopharmaceutical for SLN identification. This study also demonstrated that the number of non-radiolabeled colloidal particles and the molar dose of mannosylated compounds play a crucial role in the SLN accumulation. (C) 2004 Elsevier Inc. All rights reserved.