The Synthesis, Preliminary Animal And Clinical Studies Of F-18 Labeled Tyrosine Analogs

Positron emission tomography (PET) , which is an important tool for the clinical detection of tumors, has been widely employed all over the world. There are many kinds of PET imaging agents. The most commonly used one is ¹⁸F-FDG, which has been used in oncology for the differentiation of benign from malignant lesions, the detection and staging of malignancy, and the follow-up of therapeutic responses. However, several recent studies have demonstrated diagnostic limitations of ¹⁸F-FDG-PET such as its low specificity, no uptake in some tumor cells and appreciable uptake in inflammatory lesion. Furthermore, for brain tumor imaging, contrast between tumor tissue and normal brain is often low owing to the high glucose utilization of normal grey matter. Therefore designing and synthesizing specific and sensitive tumor imaging agents would be an important research field.The metabolism of protein will increase in cancer cells, so radiolabelled amino acids constitute another class of metabolic imaging agents which have higher specificity for differentiating inflammatory lesions from tumors, lower uptake in normal tissues, clearer images of brain tumors than those of ¹⁸F-FDG. ¹⁸F-FET is a synthetic analogue of L-tyrosine that is not metabolized in cells and does not incorporate into proteins. The increased amino acid transport into malignant cells reflects the increasing amino acid requirement in tissues. ¹⁸F-FET can be synthesized easily with relatively high radiochemical yield and has been put into clinical trial in several isolated cases, but so far there has been no such clinical report in China. We have synthesized ¹⁸F-FET with radiochemical purity of 95% which remained stable for 6 hours. A series of experiments have been carried out to seek for the optimal reaction conditions. Preclinical studies including sterility, endotoxin and toxicity tests were performed and the results accorded with the standards of Chinese Pharmacopoeia. Several brain tumor cases were studied using F-FET-PET and compared with ¹⁸F-FDG-PET. The results demonstrated that the uptake of ¹⁸F-FET in the normal brain tissues was significantly lower than that of the tumor, and the images of the brain tumor were clearer than those of ¹⁸F-FDG. So, it appears to be a very promising agent for the diagnosis of tumors.Another analogue of L-tyrosine is 6-[¹⁸F]fluoro-L-dopa which plays an important role in diagnosing Pakinson's disease. It is well known that Pakinson's disease is a progressive degenerative disease of nervous system which usually affects middle-aged and elderly...