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Synthesis and preliminary biological evaluation of a 99m Tc‐chlorambucil derivative as a potential tumor imaging agent
Author(s) -
Lin Jianguo,
Qiu Ling,
Lv Gaochao,
Li Ke,
Wang Wei,
Liu Guiqing,
Zhao Xueyu,
Wang Shanshan
Publication year - 2017
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3481
Subject(s) - chemistry , biodistribution , chlorambucil , imaging agent , technetium , spect imaging , high performance liquid chromatography , technetium 99m , radiochemistry , rhenium , nuclear medicine , chromatography , scintigraphy , nuclear chemistry , chemotherapy , biochemistry , organic chemistry , medicine , in vivo , microbiology and biotechnology , in vitro , biology , cyclophosphamide
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: 99m Tc‐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 99m Tc‐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 99m Tc‐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 99m Tc‐DPA‐CLB might be a promising SPECT imaging agent for tumor diagnosis.