Synthesis and preliminary biological evaluation of a 99mTc‐chlorambucil derivative as a potential tumor imaging agent. (7th December 2016)

• Record Type: Journal Article
• Authors: Lin, Jianguo; Qiu, Ling; Lv, Gaochao; Li, Ke; Wang, Wei; Liu, Guiqing; Zhao, Xueyu; Wang, Shanshan
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 60:Number 2(2017)
• Page Start: 116
• Page End: 123
• Publication Date: 2016-12-07
• Subjects: chlorambucil -- dipicolylamine -- SPECT -- tricarbonyl technetium/rhenium complex -- tumor imaging; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3481
• Languages: English
• ISSNs: 0362-4803

Abstract

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: 99m Tc‐DPA‐CLB (3 ) and Re‐DPA‐CLB (4 ). The high performance liquid chromatography analyses showed that the retention time of3 and4 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. Abstract : A new analog of the anticancer drug chlorambucil was synthesized after covalent bonding with the dipicolylamine chelating group. The resulting ligand DPA‐CLB was successfully radiolabeled with 99m Tc(CO)3(H2O)3 in high yield, and it is very stable in vitro and in vivo . The radiotracer has the property of favorable tumor uptake and retention, fast clearance from background and good T/NT ratios, suggesting it has potential as a tumor imaging agent for breast cancer.