Semi-automated Synthesis And Biological Evaluation Of ～(18)F-FLT

Objective: Positron emission tomography (PET) is an imaging modality for accurately determining regional function and biochemistry in vivo. PET has been used in oncology for detection and staging of malignancy, follow-up of therapeutic response and differentiation of benign and malignant lesions. 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT) appears to be one of the most promising radiopharmaceuticals for PET imaging. However, the low radiochemical yield of ¹⁸F-FLT, long chemical reaction steps in the preparation of its precursors and expensive commercially available synthesizer have been major obstacles for routine clinical use of ¹⁸F-FLT. To improve the radiochemical yield and simplify the purification system, we modified the 2-Vessel ¹⁸F-FDG module (manufactured by CTI) for producing ¹⁸F-FLT. The effects of precursor concentrations and reaction temperatures as well as precursors used on the radiochemical yield of ¹⁸F-FLT were studied. The biodistribution, radiation dosimetry of ¹⁸F-FLT in mice and the use of ¹⁸F-FLT PET imaging for detecting tumor proliferation were described.Methods: Three precursors and cold standard of ¹⁸F-FLT were synthesized using thymidine as the starting material. The parameters (such as temperatures, heat time, transfer time and so on) of 2-vessel ¹⁸F-FDG synthesis module were changed. The effects of reaction conditions and different precursors on radiochemical yield were compared. Biodistribution of tumor-bearing mice was performed when volume of the tumors ranged from 600 to 800mm³. ¹⁸F-FLT in 0.2mL isotonic saline solution was injected intravenously into normal and tumor-bearing mice. The mice were sacrificed by cervical dislocation at different time intervals postinjection. The radiation dosimetry of human was evaluated by the biodistribution data obtained from the mice. The PET imagings were obtained at 60min and 90min after administration of ¹⁸F-FLT in...