Indium-111 labeling of low density lipoproteins with the DTPA-bis(stearylamide): Evaluation as a potential radiopharmaceutical for tumor localization
Indium-111 labeling of low density lipoproteins with the DTPA-bis(stearylamide): Evaluation as a potential radiopharmaceutical for tumor localization
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DOI：
10.1021/bc950073l
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发表时间：
1996-01-01
影响因子：
4.7
通讯作者：
Nepveu, F
中科院分区：
文献类型：
--
作者：
Jasanada, F;Urizzi, P;Nepveu, F
为了利用 LDL 受体途径将放射性核素靶向癌症部位以进行成像和诊断，开发了一种使用 DTPA-双（硬脂酰胺）(L) 用 In-111 标记 LDL 的方法。这种双功能配体旨在掺入 LDL 的磷脂单层中，并特异性螯合表面的 In3+ 阳离子。配体以 65-80% 的产率掺入缓冲介质中的 LDL。通过透析检查时，L-LDL 样品在 24 小时内保持稳定，因此可以在进行铟 111 放射性标记之前进行储存。 In-L-LDL 颗粒的体外研究表明，铟标记可快速实现（1 小时）。超过 85% 的铟原子与掺入的 DTPA 衍生物的螯合功能结合，少于 10% 与 LDL 的非特异性络合位点（例如蛋白质残基）结合。在人血清中孵育后，In-L-LDL 样品的 LDL 部分 (95%) 恢复的铟活性远高于 In-LDL 样品 (35%)，表明配体具有很强的稳定螯合作用。竞争性结合研究表明，当 In-L/LDL 比率在 5 至 30 之间变化时，In-L-LDL 会像天然 LDL 一样被 A549 细胞的 LDL 受体识别。所有这些体外实验都表明 In-L-LDL 缀合物具有适合进一步进行体内实验的特性。
In order to use the LDL receptor pathway to target radionuclides to cancer sites for imaging and diagnostic purposes, a labeling procedure of LDL with In-111 using the DTPA-bis(stearylamide) (L) has been developed. This bifunctional ligand is intended to be incorporated into the phospholipid monolayer of LDL and to specifically chelate the In3+ cation at the surface. The ligand was incorporated into LDL in buffered medium with a 65-80% yield. The L-LDL samples are stable over a 24 h period when examined by dialysis, allowing their storage before indium-111 radiolabeling. In vitro studies of In-L-LDL particles show that indium labeling is rapidly achieved(1 h). More than 85% of the indium atoms are bound to the chelating functions of the incorporated DTPA derivatives and less than 10% to the nonspecific complexation sites of LDL (e.g., protein residues). After incubation in human serum, the indium activity recovered in the LDL fraction of In-L-LDL samples (95%) is much higher than in In-LDL samples (35%), pointing out the strong stabilizing chelating effect of the ligand. Competitive binding studies show that In-L-LDL are recognized by LDL receptors of A549 cells like native LDL when the In-L/LDL ratio varies from 5 to 30. All these in vitro experiments demonstrate that the In-L-LDL conjugates possess properties suitable for further work with in vivo experiments.