Synthesis and preliminary biological evaluation of a ^99mTc-chlorambucil derivative as a potential tumor imaging agent

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• 作者：Jianguo Lin ; Ling Qiu ; Gaochao Lv ; Ke Li ; Wei Wang ; Guiqing Liu ; Xueyu Zhao and Shanshan Wang
• 刊名：Journal of Labelled Compounds and Radiopharmaceuticals
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：60
• 期：2
• 页码：116-123
• 全文大小：807K
• ISSN：1099-1344

文摘

Technetium-99m-based radiopharmaceuticals have been used widely as diagnostic agents in the nuclear medicine. Chlorambucil (CLB) as one typical alkylating drug exhibits excellent inhibition effects against many human malignancies. To develop and explore a novel potential imaging agent for early diagnosis of tumors, tricarbonyl technetium-99m and rhenium complexes on the basis of the tridentate ligand dipicolylamine (DPA) bound to the chlorambucil pharmacophore were designed and synthesized: ^99mTc-DPA-CLB (3) and Re-DPA-CLB (4). The high performance liquid chromatography analyses showed that the retention time of 3 and 4 was 13.5 and 13.6 minutes, respectively. Radiolabeling efficiency of the ^99mTc-DPA-CLB tracer was 97%, and the radiochemical purity was larger than 95% after 6 hours stored in phosphate buffered saline or human serum as observed by thin layer chromatography and high performance liquid chromatography. Biodistribution studies in a mouse model of breast cancer showed ^99mTc-DPA-CLB exhibited a favorable tumor affinity. The radiotracer cleared quickly in the first hour via hepatobiliary and renal routes of excretion, resulted in a very low background at 4 hours post injection (p.i.). It had moderate uptake ratios of tumor to blood and tumor to muscle. These results suggested ^99mTc-DPA-CLB might be a promising SPECT imaging agent for tumor diagnosis.