Motaleb Mohamed A, El-Safoury Dina M, Abd-Alla Walaa H, Awad Gehanne A S, Sakr Tamer M
a Labelled Compounds Department , Hot Labs Center, Atomic Energy Authority , Cairo , Egypt.
b Pharmaceutical Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing , Misr University for Science & Technology , Giza , Egypt.
Int J Radiat Biol. 2018 Dec;94(12):1134-1141. doi: 10.1080/09553002.2019.1524945. Epub 2018 Oct 29.
Ifosfamide as a chemotherapeutic drug is used for the treatment of different cancer types. The purpose of this study is the preparation of Tc-ifosfamide complex to be evaluated as a potential candidate for tumor imaging.
The radiolabeling of ifosfamide with technetium-99m was carried out by mixing 4mg ifosfamide and 5 μg of SnCl.2HO with 400 MBq NaTcO at pH 9 for 30 min at room temperature. Computer simulation studies were performed using Accelrys Discovery Studio 2.5 operating system to illustrate the interaction of ifosfamide and Tc-ifosfamide complexes with DNA. The in-vivo biodistribution of Tc-ifosfamide was studied in tumor-bearing Albino mice.
A new Tc-ifosfamide complex was synthesized with a good radiochemical yield of 90.3 ± 2.1% under the optimized conditions and exhibited in-vitro stability up to 2 h. Biodistribution studies showed good uptake in tumor site and high uptake in tumor site with T/NT ∼3 after 60 min post-injection. Besides, the molecular docking study confirmed that the complexation of ifosfamide with technetium-99m does not abolish its binding to the target receptor.
These promising results afford a new radiopharmaceutical that could be used as a potential tumor imaging.
异环磷酰胺作为一种化疗药物用于治疗不同类型的癌症。本研究的目的是制备锝 - 异环磷酰胺复合物，以评估其作为肿瘤成像潜在候选物的可能性。
在室温下，将4mg异环磷酰胺和5μg SnCl₂·2H₂O与400MBq高锝酸钠在pH 9的条件下混合30分钟，进行异环磷酰胺与锝 - 99m的放射性标记。使用Accelrys Discovery Studio 2.5操作系统进行计算机模拟研究，以阐明异环磷酰胺和锝 - 异环磷酰胺复合物与DNA的相互作用。在荷瘤白化小鼠中研究了锝 - 异环磷酰胺的体内生物分布。
在优化条件下合成了一种新的锝 - 异环磷酰胺复合物，放射化学产率良好，为90.3±2.1%，并在体外稳定长达2小时。生物分布研究表明，注射后60分钟，肿瘤部位摄取良好，肿瘤部位摄取较高，T/NT约为3。此外，分子对接研究证实，异环磷酰胺与锝 - 99m的络合并不消除其与靶受体的结合。
这些有前景的结果提供了一种可作为潜在肿瘤成像剂的新型放射性药物。
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