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研究生:周大凱
研究生(外文):Ta-Kai Chou
論文名稱:[18F]FMISO,[18F]FDG及[18F]FAc作為正子造影探針於荷發炎及腫瘤動物模式之評估
論文名稱(外文):Evaluation of [18F]FMISO, [18F]FDG and [18F]FAc as PET probes in a mouse model bearing sarcoma and inflammatory lesion
指導教授:王信二
指導教授(外文):Hsin-Ell Wang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:放射醫學科學研究所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:71
中文關鍵詞:腫瘤發炎組織[18F]FMISO[18F]FDG[18F]FAc
外文關鍵詞:tumorinflammatory lesion[18F]FMISO[18F]FDG[18F]FAc
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背景: 2-Deoxy-2-18F-fluoro-D-glucose ([18F]FDG)為臨床上廣泛使用敏感度高但非特異性之腫瘤造影藥物;[18F]fluoromisonidazole ([18F]FMISO)為缺氧組織造影劑;[18F]fluoroacetate ([18F]FAc)則被視為有潛力取代[11C]acetate之腫瘤造影劑。[18F]FDG可積聚於發炎組織已有多篇文獻提及,但[18F]FMISO與[18F]FAc是否亦會積聚於發炎組織?目前尚無文獻報導。本研究以荷腫瘤與發炎組織之小鼠為實驗動物,比較此三種藥物([18F]FDG、[18F]FMISO以及[18F]FAc)於此動物模式上之生物分布,以釐清[18F]FMISO及[18F]FAc在發炎組織的積聚情況。
材料與方法:[18F]FMISO與[18F]FAc之合成方法均參考文獻並稍作修改。[18F]FMISO之放射化學產率為20%~25% (decay corrected),放射化學純度大於90%,[18F]FAc為35%~40% (decay corrected),放射化學純度大於95%;[18F]FDG 由自動合成器合成。C3H小鼠於第0天於右後腿種植入2 x 105 之KHT sarcoma 腫瘤細胞,並於第11天於左後腿打入0.1 mL turpentine oil誘發發炎。生物分布實驗、藥物動力學評估及微正子電腦斷層掃描均於腫瘤細胞種入後第14天進行。
結果:於turpentine oil 皮下注射後三天可清楚由[18F]FDG/microPET 影像及autoradiography觀察確認發炎組織。各類放射藥物注射後4小時,由microPET影像所得之腫瘤/肌肉比與發炎/肌肉比,[18F]FDG為8.13與4.66 (n=3);[18F]FMISO為6.93與1.53 (n=6);[18F]FAc則為3.80與3.25 (n=6)。三者之腫瘤/發炎比以[18F]FMISO為最高(4.63),[18F]FDG與[18F]FAc分別為1.75及1.18。藥物於體內之分佈相半衰期(t1/2α)與排除相半衰期(t1/2β):[18F]FMISO分別為0.09與1.08小時,[18F]FDG為0.05與5.05小時,[18F]FAc則為0.15與11.33小時。血液中AUC (area under curve)分別為11.78、12.41與116.23 h x %ID/g。AUC 結果顯示[18F]FAc於動物體內有最高之生物可用性。
結論:MicroPET影像及生物分布顯示[18F]FDG與[18F]FAc二者均顯著積聚於腫瘤及發炎組織;對[18F]FMISO而言,於注入藥物後4小時腫瘤積聚量明顯高於發炎組織。三類藥物中[18F]FMISO積聚於發炎組織之絕對量最低。本研究結果指出[18F]FMISO於本動物模式中具分辨發炎與腫瘤組織之潛力。
Objectives: 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was generally considered a sensitive but not specific probe for tumor imaging. [18F]fluoromisonidazole ([18F]FMISO) was regarded as a hypoxia imaging agent. [18F]fluoroacetate ([18F]FAc) was proposed as a possible alternative to [11C]-acetate and is also applied as a tumor imaging agent. Accumulation of [18F]FDG in inflammatory lesion was well documented, while that of [18F]FMISO and [18F]FAc was not. This study compared the biodistribution of the three tracers in a sarcoma- and inflammatory lesion- bearing mouse model.
Methods: Radiosynthesis of [18F]FMISO and [18F]FAc were slightly modified from previous report. The decay-corrected radiochemical yields of [18F]FMISO and [18F]FAc were 20%~25% and 35%~40%, respectively. The radiochemical purity was greater than 90% for [18F]FMISO and 95% for [18F]FAc. C3H mice were inoculated with 2x105 KHT sarcoma cells in the right thigh on day 0. Turpentine oil (0.1mL ) was injected in the left thigh on day 11 to induce inflammatory lesion. Biodistribution, pharmacokinetics and microPET imaging of the three tracers were performed on day 14 after tumor inoculation.
Results: The inflammatory lesions was clearly visualized by [18F]FDG/microPET and autoradiography at 3 days after turpentine oil injection. Derived from microPET image, the tumor-to-muscle (Tu/Mu) and inflammatory lesion-to-muscle (Inf/Mu) ratios were 8.13 and 4.66 for [18F]FDG (n=3), 6.93 and 1.53 for [18F]FMISO (n=6), and 3.80 and 3.25 for [18F]FAc (n=6) at 4 hr post injection. Among these, the tumor-to-inflammatory lesion ratio was highest for [18F]FMISO (4.63) compared with that of [18F]FDG (1.75) and [18F]FAc (1.18). The distribution half-life (t1/2α) and the elimination half-life (t1/2β) were 0.09 hr and 1.08 hr for [18F]FMISO, 0.05 hr and 5.05 hr for [18F]FDG, and 0.15 hr and 11.33 hr for [18F]FAc in mice. The area under curve (AUC) is 11.78, 12.41 and 116.23 hr ´ %ID/g for [18F]FMISO, [18F]FDG and [18F]FAc, respectively. The AUC showed the highest bioavailability of [18F]FAc among these traces in mice.
Conclusions: MicroPET images showed that [18F]FDG and [18F]FAc delineated both tumor and inflammatory lesion while [18F]FMISO accumulated in tumor significantly higher than that in inflammatory lesion at 4 hr post injection. The uptake of [18F]FMISO in inflammatory lesions is lowest among these tracers. Our result demonstrated the potential of [18F]FMISO in distinguishing tumor from inflammatory lesion in a mouse model.
中文摘要 ……………………………………………………………1
英文摘要 ……………………………………………………………3
壹、 前言 …………………………………………………………..5
貳、 材料與方法 …………………………………………………..9
一. 材料 ………………………………………………………...9
二. 方法 ……………………………………………………….13
1. [18F]FMISO標記前驅物(2’-Nitro-1’-imidazolyl)-2-O-acetyl-3-O-tosylpropanol之合成
2. FMISO標準品之合成
3. [18F]FMISO之放射性同位素標幟
4. [18F]FAc之放射性同位素標幟
5. KHT sarcoma 細胞株之細胞培養
6. 荷腫瘤與發炎小鼠動物模式之建立
7. [18F]FDG於荷腫瘤與發炎小鼠之microPET image及whole body autoradiography
8. [18F]FDG、[18F]FMISO及[18F]FAc於荷腫瘤與發炎小鼠之microPET造影
9. [18F]FDG、[18F]FMISO及[18F]FAc於荷腫瘤與發炎小鼠之生物分布研究

10. [18F]FDG、[18F]FMISO及[18F]FAc於荷腫瘤與發炎小鼠之藥物動力學評估
參、 結果…………………………………………………………..31
1. [18F]FMISO標記前驅物之合成
2. FMISO標準品之合成
3. [18F]FMISO之放射性同位素標幟
4. [18F]FAc之放射性同位素標幟
5. [18F]FDG於荷腫瘤與發炎小鼠之microPET image及whole body autoradiography
6. [18F]FDG、[18F]FMISO及[18F]FAc於荷腫瘤與發炎小鼠之microPET造影
7. [18F]FDG、[18F]FMISO及[18F]FAc於荷腫瘤與發炎小鼠之生物分布研究
8. [18F]FDG、[18F]FMISO及[18F]FAc於荷腫瘤與發炎小鼠之藥物動力學評估
肆、 討論………………………………………………………….53
伍、 結論………………………………………………………….62
陸、 參考文獻…………………………………………………….63
1. Cher, L. M., C. Murone, Lawrentschuk. N, Ramdave. S, Papenfuss. A, Hannah. A, O’Keefe. G. J, Sachinidis. J. I, Berlangieri. S. U, Fabinyi. G, Scott. A. M. Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies. J Nucl Med 2006;47(3):410-418
2. Bar-Shalom, R., A. Y. Valdivia. PET imaging in oncology. Semin Nucl Med 2000;3:150-185
3. Avril, N. GLUT1 expression in tissue and 18F-FDG uptake. J Nucl Med 2004;45(6):930-932
4. Strauss, L. G. Fluorine-18 deoxyglucose and false-positive results: a major problem in the diagnostics of oncological patients. Eur J Nucl Med 1996;10:1409-1415
5. Rajendran, J. G. and K. A. Krohn. Imaging hypoxia and angiogenesis in tumors. Radiol Clin North Am 2005;1:169-187
6. Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy.Br J Radiol 1953;26:638–648
7. Harris AL. Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer 2002;2:38–47
8. Sorger, D., M. Patt, P. Kumar, L.I. Wiebe, H. Barthel, A. Seese, C. Dannenberg, A. Tannapfel, R. Kluge, O. Sabri. [18F]Fluoroazomycinarabinofuranoside (18FAZA) and [18F]Fluoromisonidazole (18FMISO): a comparative study of their selective uptake in hypoxic cells and PET imaging in experimental rat tumors. Nucl Med Biol 2003;30(3):317-326
9. Martin, G. V., J. H. Caldwell, Rasey. J. S, Grunbaum. Z, Cerqueira. M, Krohn. K. A. Enhanced binding of the hypoxic cell marker [3H]fluoromisonidazole in ischemic myocardium. J Nucl Med 1989;30(2):194-201
10. R.S. Liu. Clinical application of [C-11]acetate in oncology. Clinical Positron Imaging 2000;3:18B
11. Lear, J. L. and R. F. Ackermann. Evaluation of radiolabeled acetate and fluoroacetate as potential tracers of cerebral oxidative metabolism. Metab Brain Dis 1990;5:45-56
12. Kallman, R. F. The phenomenon of reoxygenation and its implications for fractionated radiotherapy. Radiology 1972;105:135-142
13. Abdallah C, David J.Y, Wayne T, E.Edmund Kim, Sidney Wallace. Rapid Synthesis of 3-[18F]Fluoro-1-(2’-Nitro-1’-Imidazolyl)-2-Propanol ([18F]Fluoromisonidazole).Pharmaceutical Research 1994;11:466-469
14. K. Hamacher, H.H Coenen. Efficient routine production of the 18F-labeled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine. Applied Rad and iso 2002;57:853-856
15. Grierson, J. R., J. M. Link, C. A. Mathis, J. S. Rasey, K. A. Krohn. A radiosynthesis of fluorine-18 fluoromisonidazole. J Nucl Med 1989;30:343-350
16. Sykes, T. R., T. J. Ruth, M.J. Adam. Synthesis and murine tissue uptake of sodium [18F]fluoroacetate. Int J Rad Appl Instrum B 1986;13:497-500
17. Chang, C. H., H. E. Wang, S.Y. Wu, K.H. Fan, T.H. Tsai, T.W. Lee, S.R. Chang, R.S. Liu, C.F. Chen, C.H. Chen, Y.K. Fu. Comparative evaluation of FET and FDG for differentiating lung carcinoma from inflammation in mice. Anticancer Res 2006;26(2):917-925
18. van Waarde, A., D. C. Cobben, A. J. Suurmeijer, B. Maas, W. Vaalburg, E. F. De Vries, P. L. Jager, H. J. Hoekstra, P.H. Elsinga. Selectivity of 18F-FLT and 18F-FDG for differentiating tumor from inflammation in a rodent model J Nucl Med 2004;45:695-700
19. P. Kumar, D. Stypinski, H. Xia, A.J.B. McEwan, H.-J. Machulla, L.I. Wiebe. Fluoroazomycin arabinoside (FAZA): Synthesis, 2H and 3H-labeling and preliminary biological evaluation of a novel 2-nitroimidazole marker of tissue hypoxia. J Label Compd Radiopharm 1999;42:3-16
20. Gronroos, T., L. Bentzen, P. Marjamaki, R. Murata, M.R. Horsman, S. Keiding, O. Eskola, M. Haaparanta, H. Minn, O. Solin. Comparison of the biodistribution of two hypoxia markers [18F]FETNIM and [18F]FMISO in an experimental mammary carcinoma. Eur J Nucl Med Mol Imaging 2004;31:513-520
21. Pellegrino D, Bonab AA, Dragotakes SC, Pitman JT, Mariani G and Carter EA: Inflammation and infection: imaging properties of 18F-FDG-labeled white blood cells versus 18F-FDG. J Nucl Med 2005;46:1522-1530
22. Yamada, S., K. Kubota, R. Kubota, T. Ido, N. Tamahashi. High accumulation of fluorine-18-fluorodeoxyglucose in turpentine-induced inflammatory tissue. J Nucl Med 1995;36:1301-1306
23. Oyama N, Ponde DE, Dence CS, Yokoyama O, Siegel BA, Welch ML. In vitro and in vivo assessment of F-18 fluoroacetate; a potential analog for tumor imaging. J Nucl Med 2004;45:331P
24. Lim, J. L. and M. S. Berridge . An efficient radiosynthesis of [18F]fluoromisonidazole. Appl Radiat Isot 1993;44:1085-1091
25. Sun, L. Q., T. Mori, C.S. Dence, D.E. Ponde, M.J. Welch, T. Furukawa, Y. Yonelura, Y. Fujibayashi. New approach to fully automated synthesis of sodium [18F]fluoroacetate -- a simple and fast method using a commercial synthesizer. Nucl Med Biol 2006;33(1):153-158
26. Ponde DE, Oyama N, Dence CS, Welch MJ. [18F]fluoroacetate, an analog of C-11 acetate for tumor imaging. J Nucl Med 2003;44:1062P
27. Brizel, D. M; Rosner, G. L; Harrelson, J; Prosnitz, L. R; Dewhirst, M. W. Pretreatment oxygenation profiles of human soft tissue sarcoma. Int. J. Radia. Oncol. Biol. Phys 1994;30:635-642
28. Gatenby, R. A; Kessler, H. B; Rosenblum, J. S; Coia, L. R; Moldofsky, P. J; Hartz, W. H; Broder, G. J. Oxygen distribution in squmous cell carcinoma metastases and its relationship to outcome of radiation therpy. Int. J. Radiat. Oncol. Biol. Phys 1988;14:831-838
29. Hockel, M., C. Knoop, C. Schlenger, K. Vorndran, B. Baubmann, E. Mitze, M. Knapstein, P.G. Vaupel. Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 1993;26:45-50
30. Hockel, M., K. Schlenger, K. Knoop, C. Vaupel, P. Oxygenation of carcinomas of the uterine cervix: evaluation by computerized O2 tension measurements. Cancer Res 1991;51:6098-6102
31. Hockel, M., B. Vorndran, K. Baubmann, E. Knapstein, P.G. Tumor oxygenation: a new predictive parameter in locally advanced cancer of the uterine cervix. Gynecol Oncol 1993;51:141-149
32. Lartigau, E., A. M. Le Ridant, P. Weeger, P. Mrtin, L. Sigal, R. Lusinchi, A. Luboinski, B. Eschwege, F. Guichard, M. Oxygenation of head and neck tumors. Cancer 1993;71:2319-2325
33. Tochon-Danguy, H. J., J. I. Sachinidis, Chan. F, Chan. J. G, Hall. C, Cher. L, Stylli. S, Hill. J, Kaye. A, Scott. A. M. Imaging and quantitation of the hypoxic cell fraction of viable tumor in an animal model of intracerebral high grade glioma using [18F]fluoromisonidazole (FMISO). Nucl Med Biol 2002;29(2):191-197
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