[～(18)F]Fluorocholine Analogues: Synthesis And Application In Tumor Imaging

Purpose: Positron emission tomography (PET) is an imaging modality for accurately determining regional function and biochemistry within various organs of the human body. PET has been used in oncology for the detection and staging of malignancy, follow-up of therapeutic response, and differentiation of benign from malignant lesions. [18F]FDG is the most widely used imaging agent in oncology. Although FDG-PET is an excellent tool in the management of oncologic patients, it is not without problems and potential pitfalls. [18F] FDG is a nonspecific metabolic agent that mainly reflects glucose metabolism and increased anaerobic glucosis that take place in malignant tumors. This nonspecific increased [18F] FDG accumulation may be misguiding at times such as in the presence of nonspecific inflammation or acute inflammatory reaction. Some tumors can not be detected with [18F]FDG. Therefore finding a metabolic agent that is more specific than [18F] FDG would be a major step forward.Choline is a quaternary ammonium base. All cells utilize choline as a precursor for the biosynthesis of phospholipids. Carcinogenesis is characterized by enhanced cell proliferation. It is known that rapidly proliferating tumors contain large ammonts of phospholipid, particularly phosphatidylcholine. [11C]choline was used to detect brain tumor and prostate cancer, in which the sufficiently high tumor to normal tissue and tumor to blood radioactivity ratios suggest that this 11C-tracer was a potentially useful tumor imaging agent. However, the half-life of 11C (20min) limits its use in tumor detection. In order to overcome the shortcoming of "C, we synthesized [18F] fluorocholine and its analogues in order to evaluate them in tumor imaging.Method: Fluorocholine was prepared by two methods: (1) CH2(OTs)2 reacted with Bu4NF or KF/K222 to give CH2F-OTs,which was treated with dimethylamino- ethanol to formed fluorocholine. (2) CH2Br2 reacted with KF/K222, followed by treating with dimethylaminoethanol to form fluorocholine. Fluoroethylcholine was prepared by similar...