Hina Saira, Bokhari Tanveer Hussain, Roohi Samina, Rajoka Muhammad Ibrahim, Sohaib Muhammad
Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan / Department of Zoology, Government College Woman University, Faisalabad, Pakistan.
Department of Chemistry, Government College University, Faisalabad, Pakistan.
Pak J Pharm Sci. 2018 Mar;31(2):517-524.
Epirubicin is an antineoplastic agent of anthracycline antibiotic, used for treating a variety of tumor types such as lymphoma, cancer of the breast, lung, ovary and stomach. The objective of this work was to demonstrate direct radiolabeling of epirubicin with Tc, quality control, biological characterization and scientigraphic evaluation in tumor bearing mice. The 99mTc-epirubicin labeling was optimized by varying the amounts of ligand 100-350μg, stannous chloride dihydride 20-50μg and pH range 2-10 by using NaOH or HCl. The radiochemical purity of Tc-epirubicin was evaluated by chromatographic techniques (Whatman No. 3 paper and ITLC-SG). HPLC analyses were performed to check purity of epirubicin and radiochemical purity of labeled Tc- epirubicin. Biodistribution and scintigraphic imaging of Tc-epirubicin was performed in normal and tumor bearing mice at various time intervals. The optimum conditions ensuring Tc-epirubicin labeling yield as high as 99% by adding 35μg SnCl.2HO, 200μg of ligand at pH 6 for 30 min at room temperature (25°C±2°C). HPLC of Tc-epirubicin shows about 99% binding of the compound with technetium-99m. Electrophoresis study indicated the neutral nature of Tc-epirubicin. Biodistribution data and scintigraphic results showed that Tc-epirubicin accumulated in the liver as well as in tumor with significant uptake and excellent retention. Tc-epirubicin shows good stability in human serum. In vitro and in vivo studies revealed the significantly uptake of Tc-epirubicin in the tumor, and also indicating the efficiency of Tc-epirubicin as a tumor diagnostic agent.
表柔比星是一种蒽环类抗生素抗肿瘤药，用于治疗多种肿瘤类型，如淋巴瘤、乳腺癌、肺癌、卵巢癌和胃癌。本研究的目的是在荷瘤小鼠中证明表柔比星与锝的直接放射性标记、质量控制、生物学特性及显像评估。通过使用氢氧化钠或盐酸改变配体100 - 350μg、二水合氯化亚锡20 - 50μg的量以及pH范围2 - 10，对99mTc - 表柔比星标记进行优化。通过色谱技术（沃特曼3号纸和ITLC - SG）评估Tc - 表柔比星的放射化学纯度。进行高效液相色谱分析以检查表柔比星的纯度和标记的Tc - 表柔比星的放射化学纯度。在正常和荷瘤小鼠的不同时间间隔进行Tc - 表柔比星的生物分布和闪烁显像。通过在室温（25°C±2°C）下添加35μg SnCl₂·2H₂O、200μg配体、pH 6条件下反应30分钟，确保Tc - 表柔比星标记产率高达99%的最佳条件。Tc - 表柔比星的高效液相色谱显示该化合物与99m锝的结合率约为99%。电泳研究表明Tc - 表柔比星呈中性。生物分布数据和闪烁显像结果表明，Tc - 表柔比星在肝脏以及肿瘤中蓄积，摄取显著且滞留良好。Tc - 表柔比星在人血清中显示出良好的稳定性。体外和体内研究表明，Tc - 表柔比星在肿瘤中有显著摄取，也表明Tc - 表柔比星作为肿瘤诊断剂的有效性。
