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三种99mTc-HIG制剂的放射化学行为及生物学效能比较

Comparison of the radiochemical behaviour and biological efficacy of three 99mTc-HIG preparations.

作者信息

Gano L, Rodrigues A, Marques E, Patrício L

机构信息

Instituto Nacional de Engenharia e Technologia Industrial, Departamento de Radioisótopos, Sacavém Portugal.

出版信息

J Nucl Biol Med (1991). 1994 Dec;38(4 Suppl 1):38-42.

PMID:7632766
Abstract

The aim of the present study was to evaluate whether the different methodologies used for human polyclonal immunoglobulin (HIG) preparation can affect the radiochemical purity of 99mTc-HIG and its binding affinity to infection sites. Three intravenous immunoglobulin preparations, beta-propiolactone treated, hydrochloric acid/pepsin treated, and an unmodified HIG molecule were studied. The HIG preparations were analysed by size-esclusion HPLC. The UV chromatogram profiles obtained showed some percentage of polymeric and dimeric fractions in all of them. The three HIG studied were directly radiolabelled via 2-mercaptoethanol reduction. Lyophilized kits containing 1 mg of HIG and a small amount of MDP(Sn) solution were prepared and then radiolabelled by adding pertechnetate-99m. The radiolabelled products, evaluated by ITLC, showed high radiochemical purity and in vitro stability. Biodistribution studies were performed in mice with an infection in the right thigh induced by the im administration of a single isolate of S. aureus, in order to compare the ability of 99mTc-HIG to detect an infectious focus. This study suggests that any damage during immunoglobulin treatment can influence the in vivo behaviour of 99mTc-HIG.

摘要

本研究的目的是评估用于制备人多克隆免疫球蛋白(HIG)的不同方法是否会影响99mTc-HIG的放射化学纯度及其与感染部位的结合亲和力。研究了三种静脉注射免疫球蛋白制剂,即经β-丙内酯处理的、经盐酸/胃蛋白酶处理的以及未修饰的HIG分子。通过尺寸排阻高效液相色谱法对HIG制剂进行分析。所获得的紫外色谱图表明,所有制剂中均存在一定比例的聚合物和二聚体组分。对所研究的三种HIG通过2-巯基乙醇还原法直接进行放射性标记。制备含有1 mg HIG和少量MDP(Sn)溶液的冻干试剂盒,然后加入99m锝酸盐进行放射性标记。通过离子交换薄层层析法评估放射性标记产物,结果显示其具有高放射化学纯度和体外稳定性。在通过肌内注射单一金黄色葡萄球菌菌株诱导右大腿感染的小鼠中进行生物分布研究,以比较99mTc-HIG检测感染灶的能力。本研究表明,免疫球蛋白处理过程中的任何损伤都可能影响99mTc-HIG的体内行为。

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