The biological study of 18F-Fluoroacetate as a PET probe & the radiochemical synthesis of radiolabeled fluorinated nucleoside analogues and study as gene imaging probes

• Main Authors: Chun-Yi Wu, 吳駿一
• Other Authors: Hsin-Ell Wang
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/06639621407080552867

碩士 === 國立陽明大學 === 放射醫學科學研究所 === 95 === The biological study of 18F-Fluoroacetate as a PET probe Abstract Objectives: [11C]acetate ([11C]Ac) has been used as a probe of tumor detection through entry into anabolic pathways as mediated by acetyl-coenzyme A. However, the short half-life of C-11 (20 min) limits its widespread usage in clinical PET applications. This study evaluated the fluorinated analog, [18F]fluoroacetate ([18F]FAc), as a PET probe for monitoring NG4TL4 sarcoma, LLC1 lung carcinoma and inflammation in different mouse models. Methods: Starting from ethyl bromoacetate, [18F]FAc was prepared by a two-step synthesis in 60 min with high yield (60%, decay corrected) and high radiochemical purity (＞98%). The cellular uptake studies of the three thymidine analogues [18F]FAc, [18F]FDG and [11C]Ac in NG4TL4 sarcoma cell lines were conducted.FVB/N mice were inoculated with 2× 105 NG4TL4 sarcoma cells in the left shoulder and C57BL/6 mice were inoculated with 2×106 LLC1 cells in the left shoulder on day 0. C57BL/6 mice were injected with 0.1 mL turpentine oil in the right shoulder and 3 days before animal experiments. Results: Cell uptake study showed that there are steady increase in the cell-to-medium ratio of 18F-FDG and 18F-FAc with time. The radioactivitie of [11C] Ac retained in NG4TL4 sarcoma cells were less than that of [18F]FAc and [18F]FDG and maintain stable within 30 min. The in vivo microPET imaging revealed that the prominent accumulation of [18F] FAc in NG4TL4 and LLC1 tumor, compared with all normal organs except bone, was observed in entire period of experiment.The radioactivity of [18F]FAc retained in the inflammatory lesion was less than that of LLC1 tumor, but still higher than most normal organs. The PET imaging with [18F]FAc and [18F]FDG both delineate tumor and inflammation. The microPET imaging showed consistent results as those from biodistribution studies. Progressive increase in bony uptake of radioactivity due to defluorination of [18F]FAc was also noted. Conclusions: The radioactivity accumulated in tumor and inflammatory lesion was both higher than most normal organs except the bone after [18F]FAc injection. This study demonstrated that [18F] FAc is a promising PET probe for detecting tumors and inflammatory tissue in our animal models. The radiochemical synthesis of radiolabeled fluorinated nucleoside analogues and study as gene imaging probes Abstract Objective: The purpose of this study was to synthesize two fluorine-18-labeled thymidine derivatives [18F]FMAU and [18F]FEAU. The biological characteristics of these two radiotracers were examined to access the feasibility of [18F]FMAU and [18F]FEAU as radio probes for HSV1-tk/GCV gene therapy. Methods: Starting from sugar-OTf, [18F]FEAU and [18F] FMAU can be prepared in 3.5 hr via a two-step synthesis. The radiochemical yield of both tracers was about 15~20% (decay corrected) and the radiochemical purity was ≧99%. The cellular uptake studies of the three thymidine analogues [18F]FEAU, [18F]FMAU and [131I]FIAU in NG4TL4-STK (tk(+)) and NG4TL4-WT (tk(-)) sarcoma cell lines were conducted. FVB/N mice bearing NG4TL4-STK (tk (+)) sarcoma in the left flank and NG4TL4-WT (tk-)) sarcoma in the left flank were enrolled for animal studies. The biodistribution study and microPET imaging of [18F]FEAU and [18F]FMAU were performed in animals bearing both tk(+) and tk(-) tumors. Results: In vitro cellular uptake of [18F]FEAU and [18F] FMAU revealed that the cell-to-medium (C/M) ratio of tk(+) cells was significantly higher than that of tk(-) cells. The cellular uptake ratio (tk(+)/tk(-)) of [18F]FEAU (141.08) was much higher than that of [18F]FMAU (7.82) after 120min incubation owing to the incorporation of [18F]FMAU into DNA in proliferating cells. The biodistribution study showed that the uptake of [18F]FEAU reached the maximum at 15 min after injection and followed a rapid clearance in most organs including tk(-) tumor except the tk(+) tumor. The tk(+)/tk(-) ratio increased with time and reached the peak (21.4) at 120 min post [18F] FEAU injection. For [18F]FMAU, not only in tk(+) tumor and urine, all the proliferative organs such as small intestine, spleen, and kidney also showed high radioactivity accumulation at 120 min after [18F]FMAU administration. Micro-PET images showed very high uptake in HSV-tk(+) tumor post [18F]FEAU injection. While for [18F]FMAU, not only the tk(+) tumor, but the tk(-) tumor and proliferation organs bowel all showed high radioactivity accumulation. The results of microPET imaging were consistent with that of biodistribution studies. Conclusion: In this study, the fluorine-18 labeled [18F] FMAU and [18F]FEAU was successfully prepared via a multi-step synthesis. The results of biodistribution studies and microPET imaging showed that [18F]FEAU is a highly promising PET probe for HSV1-tk gene imaging, while [18F]FMAU is a potential proliferation probe to access the tumor response in cancer therapy.