Anti-MUC1 aptamers: radiolabelling with 99mTc and biodistribution in MCF-7 tumour-bearing mice
Anti-MUC1 aptamers: radiolabelling with 99mTc and biodistribution in MCF-7 tumour-bearing mice
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DOI：
10.1016/j.nucmedbio.2009.04.004
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发表时间：
2009-08-01
影响因子：
3.1
通讯作者：
Missailidis, Sotiris
中科院分区：
文献类型：
--
作者：
Da Pieve, Chiara;Perkins, Alan C.;Missailidis, Sotiris
简介：先前选择的适体对蛋白质核心（AptA）或肿瘤糖基化（AptB）MUC 1糖蛋白已被缀合到MAG 2和标记的Tc-99 m，作为放射性药物的潜在用途，用于诊断乳腺cancer.Methods成像：共轭实现了高产率使用之间的氨基修饰油的适体和活化的羧基油的配体的标准肽偶联反应。MAG 2修饰的AptA对MUC 1蛋白核心的亲和力的保留使用荧光嵌入剂置换结合测定来确认。使用超滤将标记的适体与游离Tc-99 m分离，并在所有阶段通过高效液相色谱进行监测，以确保仅产生放射性标记的适体。在MCF-7荷瘤小鼠中分析并比较两种适体-放射性核素缀合物的生物分布特性。作为合成的最后一步（缀合后标记），实现了用Tc-99 m对两种适体的有效和方便的标记。两种适体-螯合剂缀合物都具有很强的Tc-99 m结合特性，并且所得复合物在体内是稳定的，无论是在核酸酶降解方面还是在金属泄漏方面。放射性标记的核酸适体表现出较高的肾清除率和较高的摄入intestin.Conclusions：AptA和AptB已成功地结合在高产量的配体MAG 2和标记的Tc-99 m。放射性标记的适体显示出不同的肿瘤摄取和清除，但在诊断使用之前需要进一步开发。(C)2009 Elsevier Inc.所有的灯都保留。
Introduction: Aptamers previously selected against the protein core (AptA) or the tumour glycosylated (AptB) MUC1 glycoprotein have been conjugated to MAG2 and labelled with Tc-99m, for the potential use as radiopharmaceuticals for diagnostic imaging of breast cancer.Methods: The conjugation was achieved in high yield using standard peptide coupling reactions between an amino modification oil the aptamer and the activated carboxylic group oil the ligands. The retention of the affinity of the MAG2 modified AptA for the MUC1 protein core was confirmed using a fluorescent intercalator displacement binding assay. The labelled aptamers were separated from free Tc-99m using Ultrafiltration and monitored by high-performance liquid chromatography at all stages, to ensure that only radiolabelled aptamers were produced, The biodistribution properties of the two aptamer-radionuclide conjugates were analysed in MCF-7 tumour bearing mice and compared.Results: Efficient and convenient labelling of the two aptamers with Tc-99m was achieved as the last step of the synthesis (post-conjugation labelling). Both the aptamer-chelator conjugates bad strong Tc-99m binding properties and the resulting complexes were stable in vivo, both in terms of nuclease degradation and leaking of the metal. The radiolabelled aptamers showed a high renal clearance and a high uptake in the intestine.Conclusions: AptA and AptB have been successfully conjugated in high yield to the ligand MAG2 and labelled with Tc-99m. The radiolabelled aptamers showed different tumour uptake and clearance, but will require further development prior to diagnostic use. (C) 2009 Elsevier Inc. All lights reserved.