Yilmaz Baris, Teksoz Serap, Kilcar Ayfer Yurt, Ucar Eser, Ichedef Cigdem, Medine Emin Ilker, Ari Kadir
Institute of Nuclear Sciences, Ege University , Izmir, Turkey .
Cancer Biother Radiopharm. 2016 Feb;31(1):14-9. doi: 10.1089/cbr.2015.1886. Epub 2016 Jan 26.
The aim of current study is to examine hydroxyurea (HU), which is an antineoplastic drug used for the treatment of leukemia, sickle-cell disease, HIV, psoriasis, thrombocythemia, and various neoplastic diseases in two aspects. The active ingredient hydroxyurea was obtained by purification of the capsule form drug, commercially named as HYDREA. Then, (99m)Tc(CO)3core radiolabeling with HU was performed as first aspect. Quality control studies of (99m)Tc(CO)3-HU complex were performed by thin-layer radiochromatography and high-performance liquid radiochromatography methods. The results demonstrated that the radiolabeling yield was quite high (98.43% ± 2.29%). Also, (99m)Tc(CO)3-HU complex has good stability during the 24-hour period. Biological behavior of (99m)Tc(CO)3-HU complex is evaluated by biodistribution studies on Wistar Albino rats. Fluorescein isothiocyanate (FITC) labeling of HU was performed as second aspect. Fluorometric evaluation of binding efficacy and fluorescence imaging studies on MCF7 and Hela cell lines were carried out. It was thought that the knowledge achieved in this study would contribute to using (99m)Tc(CO)3-HU complex as an imaging agent, which inhibits the DNA synthesis selectively, by inhibiting ribonucleotide reductase enzyme. It was observed that FITC-HU has noteworthy incorporation on both cell lines.
本研究的目的是从两个方面研究羟基脲（HU），它是一种用于治疗白血病、镰状细胞病、艾滋病、银屑病、血小板增多症和各种肿瘤疾病的抗肿瘤药物。活性成分羟基脲通过纯化商品名为HYDREA的胶囊剂型药物获得。然后，作为第一个方面，进行了[（99m）Tc（CO）3]+核心与HU的放射性标记。采用薄层层析放射色谱法和高效液相放射色谱法对（99m）Tc（CO）3-HU复合物进行质量控制研究。结果表明，放射性标记产率相当高（98.43%±2.29%）。此外，（99m）Tc（CO）3-HU复合物在24小时内具有良好的稳定性。通过对Wistar白化大鼠的生物分布研究评估（99m）Tc（CO）3-HU复合物的生物学行为。作为第二个方面，进行了HU的异硫氰酸荧光素（FITC）标记。对MCF7和Hela细胞系进行了结合效率的荧光测定评估和荧光成像研究。人们认为，本研究获得的知识将有助于将（99m）Tc（CO）3-HU复合物用作一种成像剂，该成像剂通过抑制核糖核苷酸还原酶来选择性抑制DNA合成。观察到FITC-HU在两种细胞系上都有显著的掺入。
