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研究生:盧欣怡
研究生(外文):Hsin-Yi Lu
論文名稱:硼中子捕獲治療兔VX2肝腫瘤模式之建立:BPA及PBAD-lipiodol藥物分布及藥物毒性評估
論文名稱(外文):Establishment of rabbit VX2 liver tumor model for boron neutron capture therapy : evaluate the biodistribution and toxicity of BPA and PBAD-Lipiodol
指導教授:林永昌林永昌引用關係
指導教授(外文):Yung-Chang Lin
學位類別:碩士
校院名稱:國立中興大學
系所名稱:獸醫學系
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:91
中文關鍵詞:硼中子捕獲治療兔VX2肝腫瘤模式BPAPBAD-lipiodol藥物毒性藥物分布
外文關鍵詞:Boron neutron capture therapyrabbit VX2 liver tumor modelBPAPBAD-lipiodoldrug toxicitydrug distribution
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本研究之目的為建立以硼中子捕獲治療肝腫瘤之動物模式,期以尋求有效且副作用低的新肝癌治療法。使用本實驗室已建立之兔VX2肝腫瘤模式,於藥物分布及藥物毒性學領域先評估已商品化之含硼製劑BPA是否可應用於肝癌治療,再評估新合成之含硼製劑PBAD-lipiodol於BNCT治療肝癌的可行性。並探討上述兩種藥物合併使用的效果。經頭靜脈給予125 mg/kg BPA後1~3小時為中子照射適期,腫瘤、肝臟及血液硼含量分別為5.49、4.62 ± 0.82 及4.98 ± 0.86 μg/g ,顯示BPA對於腫瘤無選擇性,毒性學方面,不管是否經中子照射均對於肝、腎和胰功能無影響;PBAD-lipiodol經由直接腫瘤內注射及肝動脈注射兩種方式給藥,兩種方法均於給藥後第4小時為中子照射適期,其腫瘤內硼濃度分別為57.41及24.93 μg/g;腫瘤與肝組織硼濃度比分別為227.77及86.52,顯示出PBAD-lipiodol對於腫瘤有高度選擇性。毒性學方面,兔隻對於直接注射有較好的耐受性,血清學及病理學較無顯著變化,經中子照射後白血球數會呈現暫時性下降;經肝動脈注射組,則會有肝指數上升的情形,另外須注意胃及十二指腸潰瘍的發生。PBAD-lipiodol成功地增加腫瘤內硼含量,雖然BPA對於腫瘤無選擇性,但仍不排除與PBAD-lipiodol併用以提升硼的微分布。
The purpose of this research is to establish an animal model for boron neutron capture therapy, looking for the new treatment meant to cure liver tumor more effectively and safely. Our method is to use the rabbit VX2 liver tumor model in which our laboratory has set up to assess the drug distribution and toxicity of commercialized boron agent BPA via intravenous injection and newly prepared boron agent PBAD-lipiodol via intra-tumoral or hepatic arterial injection. We found that the appropriate time interval for neutron irradiation was one to three hours after BPA intravenously injected. The boron concentration after BPA administrated one and half hour later in tumor , liver and blood were 5.49 , 4.62± 0.82 and 4.98 ± 0.86 μg/g, respectively. No apparent change in hepatic, renal and pancreatic functions after neutron irradiation. PBAD-lipiodol was injected into tumor directly or via hepatic artery, the optimal timing of boron concentration in the tumor was 4th hour after giving drugs, which are 57.41 and 24.93 μg/g respectively; tumor-to-liver ratio are 227.77 and 86.52 respectively. The rabbits had better tolerance in intra-tumoral injection group, their serum biochemistry and pathology had not been relatively showing the change. Their leukocyte number temporarily declined after neutron irradiation. In the hepatic arterial injection group, the liver index rises, and the stomach and duodenal ulceration occurred. We concluded that PBAD-lipiodol succeeds in increasing the content of boron in the tumor, though BPA has no selectivity to the tumor. We suggested that it does not get rid of the feasibility combined with PBAD-lipiodol in order to improve the microdistribution in tumor.
目錄 ...................................................................................................... I
圖次 ...................................................................................................... II
表次 ...................................................................................................... V
中文摘要 ...................................................................................................... VI
英文摘要 ...................................................................................................... VII
第一章 前言.............................................................................................. 1
第二章 文獻探討...................................................................................... 2
第一節 肝癌簡介....................................................................... 2
第二節 硼中子捕獲治療........................................................... 10
第三節 Lipiodol的應用............................................................. 17
第三章 材料與方法.................................................................................. 20
第一節 肝腫瘤動物模式建立................................................... 20
第二節 經頭靜脈給予BPA部分.............................................. 25
第三節 直接腫瘤內注射PBAD-lipiodol部分......................... 27
第四節 經肝動脈注射PBAD-lipiodol部分............................. 34
第四章 結果.............................................................................................. 39
第一節 肝腫瘤動物模式建立................................................... 39
第二節 經頭靜脈給予BPA部分.............................................. 40
第三節 直接腫瘤內注射PBAD-lipiodol部分......................... 42
第四節 經肝動脈注射PBAD-lipiodol部分............................. 45
第五章 討論.............................................................................................. 71
第一節 肝腫瘤動物模式建立................................................... 71
第二節 經頭靜脈給予BPA部分.............................................. 73
第三節 直接腫瘤內注射PBAD-lipiodol部分......................... 74
第四節 經肝動脈注射PBAD-lipiodol部分............................. 76
第六章 結論.............................................................................................. 79
參考文獻 ...................................................................................................... 80
吳宜潔。硼中子捕獲治療於兔肝癌模式之治療。國立中興大學碩士論文。2001。
賴汾瑩。評估含硼製劑PBA-EA-Lipiodol應用於硼中子捕獲治療兔肝癌模式之效果。國立中興大學碩士論文。2003。
Ackerman NB, Lien WM, Kondi ES, Silverman NA. The blood supply of experimental liver metastases. I. The distribution of hepatic artery and portal vein blood to ‘small’ and ‘large’ tumors. Surgery 66: 1067-1072, 1969.
Akashi Y, Koreeda C, Mizuno T, Inoue K, Kawa SKH, Tanaka Y. Hepatic parenchymal changes after the intraarterial injection of lipiodol in tumor-bearing rabbits. Investigative Radiology 28: 128~132, 1992.
Arnold MM, Kreel L, Wallace AC, Li AKC. Distribution of lipiodol and evidence for tumor necrosis in hepatocellular carcinoma. Anatomic Pathology 97: 405~410, 1992.
Baere TD, Zhang X, Aubert B, Harry G, Lagrange C, Ropers J, Dufaux J, Lumbroso J, Rougier P, Ducreux M, Roche A. Quantification of tumor uptake of iodized oils and emulsions of iodized oils: experimental study. Radiology 210: 731~735, 1996.
Barth RF, Soloway AH, Goodman JH, Gahbauer RA, Gupta N, Blue TE, Yang W, Tjarks W. Boron neutron cancer therapy of brain tumors: an emerging therapeutic modality. Neurosurgery 44: 433-451, 1999.
Barth RF, Yang W, Rotaru JH, Moeschberger ML,Boesel CP, Soloway AH, Joel DD, Nawrocky MM, Ono K, Goodman JH. Boron neutron capture therapy of brain tumors: enhanced survival and cure following blood-brain barrier disruption and intracarotid injection of sodium borocaptate and boronophenylalanine. International Journal of Radiation Oncology, Biology, Physics 47: 209-218, 2000.
Bartolozzi C, Lencioni R, Caramella D, Palla A, Bassi AM, Di Candio G. Small hepatocellular carcinoma. Detection with US, CT, MR imaging, DSA, and Lipiodol-CT. Acta Radiologica 37: 69-74,1996.
Bases RE. Uranyl protoporphyrin: a new uranium complex. Science 126: 164-165, 1957.
Bismuth H, Majno PE, Adam R. Liver transplantation for hepatocellular carcinoma. Seminars in Liver Disease 19: 311-322, 1999.
Breedis C, Young G. The blood supply of neoplasms in the liver. American Journal of Pathology 30: 969-977, 1954.
Burgener FA, Göthlin JH. Angiographic, microangiographic and hemodynamic evaluation of hepatic artery embolization in the rabbit. Investigative Radiology 13: 306-312,1978.
Chou FI, Chung HP, Shieh MS, Huang CW, Chung RJ, Yang JY, Liu HM, Kai JJ, Lui WY, Chi CW. Enhanced boron concerntration in hepatoma cells using a combination of BPA and phenylboric acid derivative entrapped lipiodol. In: Sauerwien W, Moss R, Wittig A. Research and development in neutron capture therapy. Monduzzi editore, Ferrares: 845~849, 2002.
Chou FI, Lui WY, Wei YY, Chung RJ, Kai JJ, Chi CW. Preparation and in Vitro evaluation of B-Lipiodol as boron neutron capture therapy of hepatoma. Anticancer research 19: 1759-1764, 1999.
Coderre JA, Glass JD, Fairchild RG, Roy U, Cohen S, Fand I. Selective targeting of boronophenylalanine to melanoma in BALB/c mice for neutron capture therapy. Cancer Research 47: 6377-6383, 1987.
Coderre JA, Makar MS, Micca PL, Nawrocky MM, Liu HB, Joel DD, Slatkin DN, Amols HJ. Derivations of relative biological effectiveness for the high-LET radiations produced during boron neutron capture irradiations of the 9L rat gliosarcoma in vitro and in vivo. International Journal of Radiation Oncology, Biology, Physics 27: 1121-1129, 1993.
Coderre JA, Morris GM.. The radiation biology of boron neutron capture therapy. Radiation Research 151: 1-18,1999.
Coderre JA. Boron neutron capture therapy. In: Leibel S, Phillips T (eds). Textbook of Radiation Oncology. W. B. Saunders Company, Philadelphia: 1263-1277, 1998.
Coderre JR, Button TM, Micca PL, Fisher CD, Nawrocky MM, Liu HB. Neutron capture therapy of the 9L rat gliosarcoma using the p-boronophenylalanine-fructose complex. International Journal of Radiation Oncology, Biology, Physics 30: 643-652, 1994.
Colleoni M, Audisio RA, De Brand F, Frazio N, Martinelli G, Goldhirsch A. Practical considerations in the treatment of hepatocellular carcinoma. Drugs 55: 367-382,1999.
Dickson JA, Shah SA. Technology for the hyperthermic treatment of large solid tumors at 50C. Clinics in Oncology 3:301-318, 1977.
Doria MI, Doria LK, Faintuch J, Levin B. Gastric mucosal injury after arterial infusion chemotherapy with floxuridine. A clinical and pathologic study. Cancer 73: 2042-2047, 1994.
Franco D, Capussotti L, Smadja C, Bouzari H, Meakins J, Kemeny F, Grange D, Dellepiane M. Resection of hepatocellular carcinoma. Results in 72 European patients with cirrhosis. Gastroenterology 98: 733-738, 1990.
Galasko CS, Muckle DS. Intrasarcolemmal proliferation of the VX2 carcinoma. British Journal of Cancer 29:59-65, 1974.
Gonda T, Ishida H, Yoshinaga K, Sugihara K. Microvasculature of small liver metastases in rats. The Journal of Surgical Research 94: 43-48, 2000.
Hamuro M, Nakamura K, Sakai Y, Nakada M, Ichikawa H, Fukumori Y, Yamada R. New oily agents for targeting chemoembolization for hepatocellular carcinoma. Cardiovascular and Interventional Radiology 22: 130-134,1999.
Hamuro M, Nakamura K, Sakai Y, Nakata M, Ichikawa H, Fukumori Y, Yamada R. New oily agent for targeting chemoembolization for hepatocellular carcinoma. Laboratory Investigation 22: 130~134, 1999.
Hatanaka H. Experience of boron-neutron capture therapy for malignant brain tumours--with special reference to the problems of postoperative CT follow-ups. Acta Neurochirurgica Supplementum 42: 187-92, 1988.
Hawthorne MF. New horizons for therapy based on the boron neutron capture reaction. Molecular Medicine Today: 174-181, 1998.
Hermenek P, Sobin LH. UICC TNM classification of malignant Tumors, 4th ed. Berlin, Springer Verlag, 1992.
Honjo I, Matsumura H. Vascular distribution of hepatic tumors. Experimental study . Reviews of International Hepatology 15: 681-690, 1965.
Ichihashi M, Nakanishi T, Mishima Y. Specific killing effect of 10B1-para-boronophenylalanine in thermal neutron capture therapy of malignant melanoma: in vitro radiobiological evaluation. The Journal of Investigative Dermatology 78: 215-218, 1982.
Iwai K. Maeda H, Konno T, Matsumura Y, Yamashita R, Yamasaki K, Hirayama S, Miyauchi Y. Tumor targeting by arterial administration of lipids: rabbit model with VX2 carcinoma in the liver. Anticancer Research 7: 321-328, 1987.
Javid M, Brownell GL, Sweet WH. The possible use of neutron-capturing isotopes such as boron 10 in the treatment of neoplasms. II. Computation of the radiation energies and estimates of effects in normal and neoplastic brain. The Journal of Clinical Investigation 31: 604-610, 1952.
Joel DD, Coderre JA, Micca PL, Nawrocky MM. Effect of dose and infusion time on the delivery of p-boronophanylalanine for neutron capture therapy. Journal of Neuro-Oncology 41: 213-221, 1999.
Kan Z. Dynamic study of iodized oil in the liver and blood supply to hepatic tumors. Acta Radiological Supplementum 37: 7-25, 1996.
Kew MC. Epidemiology of hepatocellular carcinoma. Toxicology 181-182: 35-38, 2002.
Kim DK, Kinne DW, Fortner JG. Occlusion of the hepatic artery in man. Surgery, Gynecology & Obstetrics 136: 966-968, 1973.
Knock FE. Perfusion of uranium-antibody complexes for the neutron capture therapy of tumors. Surgery, Gynecology & Obstetrics 109: 445-449, 1959.
Konno T, Maeda H, Iwai K, Maki S, Tashiro S, Uchida M, Miyauchi Y. Selective targeting of anti-cancer drug and simultaneous image enhancement in solid tumors by arterially administrated lipid contrast medium. Cancer 54: 2367-2374, 1984.
Kónya A, Wright KC, Szwarc IA, Collins RD. Technical aspects of catheter-related interventions in the liver of the rabbit. Acta Radiologica 38: 332-334, 1997.
Kuruppu D, Christophi C, Maeda H, O’Brien PE. Changes in the microvascular architecture of colorectal liver metastases following the administration of SMANCS/Lipiodol. Journal of Surgical Research 103:47-54, 2002.
Lin WY, Chi CW, Ho Y, Wu IC, Chung YT, Chen SD, Chou FI, Kai JJ, Lui WY, Chen TJ, Lin YC. Boron-lipiodol: a potential new drug for the treatment of liver tumors. Anticancer Research 22: 3989-3992, 2002.
Liver cancer study group of Japan. The general rules for the clinical and pathological study of primary liver cancer. Japanese Journal of Surgery 19: 98-129, 1989.
Llovet JM, Bruix J, Gores GJ. Surgical resection versus transplantation for early hepatocellular carcinoma: clues for the best strategy. Hepatology 31: 1019-1021, 2000.
MacSween RNM, Burt AD, Portmann BC, Ishak KG, Scheuer PJ, Anthony PP. Tumors and tumor-like lesions of the liver and biliary tract: aetiology, epidemiology and pathology. In: Pathology of the liver 4th ed. Churchill Livingstone, London: 711-776, 2002.
Maki S, Konno T, Maeda H. Image enhancement in computerized tomography for sensitive diagnosis of liver cancer and semiquantitation of tumor selective drug targeting with oil contrast medium. Cancer 56: 751-757, 1985.
Mclaughlin CA, Chiasson RB. The digestive system. In: Laboratory anatomy of the rabbit 3rd ed. McGraw-Hill Higher Education, United States of America: 59-64,1990.
Mehta SC, Lu DR. Targeted drug delivery for boron neutron capture therapy. Pharmaceutical Research 13: 344-351, 1996.
Nakakuma K, Tashiro S, Hiraoka T, Uemura K, Konno T, Miyauchi Y, Yokohama I. Studies on anticancer treatment with an oily anticancer drug injected into the ligated feeding hepatic artery for liver cancer. Cancer 52: 2193-2200, 1983.
Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, Kakajima Y, Ohnishi K. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 56: 918-928, 1985.
Palma LD, Pozzi-Mucelli RS. Computed tomography and magnetic resonance imaging in diagnosing hepatocellular carcinoma. Italian Journal of Gastroenterology 24: 87-91, 1992.
Palma LD. Diagnostic imaging and interventional therapy of hepatocellular carcinoma. British Journal of Radiology 71: 808-818, 1998.
Pignata S, Daniele B, Gallo C, De Vivo R, Monfardini S, Perrone F. Endocrine treatment of hepatocellular carcinoma. Any evidence of benefit? European Journal of Cancer 34: 25-32, 1998.
Pignol JP, Oudart H, Chauvel P, Sauerwein W, Gabel D, Prevot G. Selective delivery of 10B to soft tissue sarcoma using 10B-L-boronophenylalanine for boron neutron capture therapy. British Journal of Radiology 71: 320-323, 1998.
Risse JH, Grünwald F, Kersjes W, Strunck H, Caselmann WH, Palmedo H, Bender H, Biersack HJ. Intraarterial HCC therapy with I-131-lioiodol. Cancer Biotherapy & Radiopharmaceuticals 15: 65-70, 2000.
Rous P, Beard JW. Progression to carcinoma of virus-induced rabbit papillomas (Shope). The Journal of Experimental Medicine 62: 523-534, 1935.
Shike M, Gillin JS, Kemeny N, Daly JM, Kurtz RC. Severe gastroduodenal ulcerations complicating hepatic artery infusion chemotherapy for metastatic colon cancer. American Journal of Gastroenterology 81: 176-179, 1986.
Shop RE, Hurst EW. Infectious papillomatosis of rabbits: with a note on the histopathology. The Journal of Experimental Medicine 58: 607-624, 1933.
Smith DR, Chandra S, Coderre JA, Morrison GH. Ion microscopy imaging of 10B from p-boronophenylalanine in a brain tumor model for boron neutron capture therapy. Cancer Research 56: 4302-4306, 1996.
Soloway AH, Tjarks W, Barnum BA, Rong FG, Barth RF, Codogni IM, Wilson JG. The chemistry of neutron capture therapy. Chemical Reviews 98: 1515-1562, 1998.
Soloway AH, Whitmen B, Messer JR. Penetration of brain and brain tumor by aromatic compounds as a function of molecular substituents. The Journal of Pharmacology and Experimental Therapeutics 129: 310-314, 1960.
Suzuki M, Masunaga SI, Kinashi Y, Takagaki M, Sakurai Y, Kobayashi T, Ono K. The effects of boron neutron capture therapy on liver tumors and normal hepatocytes in mice. Japanese Journal of Cancer Research 91: 1058-1064, 2000.
Suzuki M, Sakurai Y, Masunaga S, Kinashi Y, Nagata K, Ono K. Dosimetric study of boron neutron capture therapy with borocaptate sodium/Lipiodol emulsion for treatment of multiple liver tumors. International Journal of Radiation Oncology, Biology, Physics 58: 892-896, 2004.
Tabaru K, Konno T, Oda T, Nagamitsu A, Ishimaru Y, Kitamura N. Treatment of VX2 carcinoma implanted in the liver with arterial and intraperitoneal administration of oily anticancer agents. Cancer Chemotherapy and Pharmacology 47: 149-154, 2001.
Thorstensen O, Isberg B. Experimental tissue transplantation using a biopsy instrument and radiologic methods. Investigative Radiology 29: 469-471, 1994.
Tolpin EI, Wellum GR, Dohan FC Jr, Kornblith PL, Zamenhof RG. Boron neutron capture therapy of cerebral gliomas. II. Utilization of the blood-brain barrier and tumor-specific antigens for the selective concentration of boron in gliomas. Oncology 32: 223-246, 1975.
Yang W, Barth RF, Rotaru JH, Moeschberger ML, Joel DD, Nawrocky MM, Goodman JH, Soloway AH. Boron neutron capture therapy of brain tumors: enhanced survival following intracarotid injection of sodium borocaptate with or without blood-brain barrier disruption. International Journal of Radiation Oncology, Biology, Physics 37: 663-672, 1997.
Young S, Hollenberg NK. Selective catheterization for magnification angiography of internal spermatic and proper hepatic arteries in rabbits. Investigative Radiology 12: 256-258, 1977.
Yu AS, Keeffe EB. Management of hepatocellular carcinoma. Reviews in Gastroenterological Disorders 3: 8-24, 2003.
Yumoto Y, Jinno K, Inatsuki S, Moriwaki S, Hanafusa T, Yumoto E, Shiota T, Higashi T, Koide N, Hada H, Murase K, Hamamoto K. Treatment of hepatocellular carcinoma by transcatheter hepatic arterial injection of radioactive iodized oil solution. Cancer Chemotherapy and Pharmacology 31: S128-S136, 1992.
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