Studies On Tumor-targeting Positron Emission Computed Tomography Tracer Containing Sulfonamide Group

Positron emission computed tomography(PET) isanoninvasive imaging technology ofanatomical morphologybased on function, metabolism and receptor-mediated for human beings in vivo, and then currently one of the best methods for clinical diagnosis andguidance of the treatment of tumors. At present, the commonly clinical usedPET tracers havesome limitationsincluding weak tumor-specific selectivity and tumor-targeting property, poor imaging contrast in tumor, misdiagnosis frequently, long and tough synthetic process,and so on.It is normally necessary to introduce novelnon-toxic water-soluble tumor-targeting PET tracers in the body.1. In the thesis, the principle and advantages of PET and the classification and research progress of PET tracers were reviewed in detail herein.Sulfanilamide and its derivatives were also introduced in the performance of specific affinity to tumors.2. 1,4,7-Triazacyclodecane-1,4,7-triacetic acid(NOTA)was synthesized by the protection,cyclization and deprotection reactionswithp-toluene sulfonyl chloride, ethylenediamine and diethanolamine as starting materials by classic Richman-Atkins method. 18F-Al-NOTA-SN was also prepared by condensationreaction between NOTA and sulfanilamide andsubsequentlycHeLation reaction with 18F- and AlCl3. These compounds were characterized by 1H NMR, UV, FT-IR,MS, etc.18F-Al-NOTA-SN was further analyzed and purified by HPLC. These results indicated that 18F- labeled process of F-Al method and the purifyprocess spent 20 and 45 minutes, respectively. The 18F- labeled ratio was 92.3%, radiochemical puritywas over 95% and radioactivity of 18F-Al-NOTA-SN was 24 mCi. Therefore, 18F-Al-NOTA-SN can be further used as a PET tracer to do the cell experiments in vitro and PET imaging in vivo.3. Thein vitroand in vivo propertiesof 18F-Al-NOTA-SN were evaluated herein. The biological experiments included the biological stability, cell uptake of normal cells and tumor cells, cell cytotoxicity, biodistribution and PET imaging in normal BALB/c-nu female mice and BALB/c-nu female mice with HeLa tumors in vivo. Experiment results demonstrated that18F-Al-NOTA-SN possessed the good biological stabilityin vitroand in vivo, lowcell cytotoxicity, high uptake by tumor cells, good tumor-targeting property and enhanced contrast PET images of tumors.The cell uptakes of normal renal epithelial cells(T293) and kidney cells of African green monkey(COS-7) were lower than that of tumor cellsincluding cervical cancer cells(HeLa), hepatoma carcinoma cells(HepG-2) and breast cancer cells(231). 18F-Al-NOTA-SN had the higher cell cytotoxicities to tumor cellsincluding HeLa, HepG-2 and 231 tumor cells than that of 293 T and COS-7 normal cells.Meanwhile,18F-Al-NOTA-SN can beexcreted by the liver andkidneys. PET signal intensities of HeLa tumorsin mice injected with 18F-Al-NOTA-SN were obviously enhanced, the portions of HeLa tumors were brighter and their demarcations became clearer during the detection time, while those of the surrounding tissues, such as the muscle, bone and blood vascular system, showed a little change. Moreover, PET signal enhancements in HeLa tumors can be obviously inhibited by the reinjection of NOTA-SN containing sulfanilamide group. Compared with the commonly clinical usedPET tracer18F-fluorodeoxyglucose(18F-FDG), 18F-Al-NOTA-SN showedhigher contrast enhancements of PET images in HeLa tumors under nopreoperativefasting conditions.Therefore18F-Al-NOTA-SN can beselectively taken up by tumors and usedas a potential radioactive tracer inPET to tumors.