Synthesis, in silico and biodistribution studies of a novel 47Sc-radiolabeled α-amino acid ester derivative attached to pyrazine and tetrazole rings for tumor targeted radiotherapy

IF 1.4 3区 化学 Q4 CHEMISTRY, INORGANIC & NUCLEAR
Mohamed A. Gizawy, Hesham A. Shamsel-Din, Mohsen M. T. El-Tahawy, Ayman A. Ibrahim
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Abstract

Recently, tumor-targeted radionuclide therapy has gained much recognition for the treatment of metastasized cancer. There is a growing interest in using the theranostic radionuclide 47Sc, owing to its excellent chemical and nuclear properties. However, the available chelating agents require a relatively high temperature for their radiolabeling, which could denature biomolecules. The aim of the present study is to synthesize a dipeptide agent that forms a thermodynamically more stable complex with 47Sc at room temperature. A novel α-amino acid ester derivative attached to pyrazine and tetrazole heterocyclic rings has been prepared by the azide coupling method. Different spectroscopic methods (FT-IR, 1H NMR, and mass spectra) were used for characterization of the target compound. The newly synthesized dipeptide was radiolabeled with 47Sc, and a high radiochemical yield of 98.5 ± 1.5 % and in vitro serum stability up to 72 h were attained at room temperature within 20 min. The quantum chemical calculations at B3PW91/6-31G(d) level were employed to establish the molecular structure of the dipeptide and its complexation with 47Sc. The selectivity of 47Sc-dipeptide toward localization in tumor cells was performed by molecular docking on different receptors in addition to in vivo biodistribution on solid tumor-bearing mice. A high T/NT ratio of 8.16 was obtained after 4 h p.i, suggesting that this complex could be used as a potential cancer theranostic agent.
用于肿瘤靶向放射治疗的新型 47Sc 放射标记α-氨基酸酯衍生物的合成、硅学和生物分布研究
最近,肿瘤靶向放射性核素疗法在治疗转移性癌症方面获得了广泛认可。由于 47Sc 具有优异的化学和核特性,人们对使用治疗放射性核素的兴趣与日俱增。然而,现有的螯合剂需要在相对较高的温度下进行放射性标记,这可能会使生物大分子变性。本研究的目的是合成一种能在室温下与 47Sc 形成热力学上更稳定的复合物的二肽剂。本研究采用叠氮偶联法制备了一种新型α-氨基酸酯衍生物,该衍生物附着在吡嗪和四唑杂环上。目标化合物的表征采用了不同的光谱方法(傅立叶变换红外光谱、1H NMR 和质谱)。用 47Sc 对新合成的二肽进行了放射性标记,在室温下 20 分钟内达到了 98.5 ± 1.5 % 的高放射化学收率和长达 72 小时的体外血清稳定性。通过 B3PW91/6-31G(d) 水平的量子化学计算,建立了二肽的分子结构及其与 47Sc 的复合物。除了在实体瘤小鼠体内的生物分布外,还通过与不同受体的分子对接研究了 47Sc 二肽在肿瘤细胞中的定位选择性。4 h p.i后,T/NT比值高达8.16,这表明该复合物可用作一种潜在的癌症治疗剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Radiochimica Acta
Radiochimica Acta 化学-核科学技术
CiteScore
2.90
自引率
16.70%
发文量
78
审稿时长
6 months
期刊介绍: Radiochimica Acta publishes manuscripts encompassing chemical aspects of nuclear science and technology.
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