title: Synthesis and preliminary biological evaluation of a99mTc-chlorambucil derivative as a potential tumor imaging agent.
abstract: 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 the99mTc-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 showed99mTc-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 suggested99mTc-DPA-CLB might be a promising SPECT imaging agent for tumor diagnosis.
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Lin
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China.
authors.forename: Gaochao
authors.initials: G
authors.lastname: Lv
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China.
authors.forename: Guiqing
authors.initials: G
authors.lastname: Liu
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China.
authors.forename: Xueyu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D002699:Chlorambucil / Q000737:chemistry*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging*; D010848:Picolinic Acids / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D065667:Renal Elimination; D013667:Technetium / Q000737:chemistry*
chemical_list: C501847:2,2'-dipicolylamine; D000588:Amines; D010848:Picolinic Acids; D019275:Radiopharmaceuticals; D002699:Chlorambucil; D013667:Technetium
keywords: SPECT; chlorambucil; dipicolylamine; tricarbonyl technetium/rhenium complex; tumor imaging