本研究之目的為建立骨肉瘤細胞與動物腫瘤模式，探討以硼酸水溶液為含硼藥物進行硼中子捕獲治療(Boron neutron capture therapy, BNCT)對骨肉瘤之療效和生物效應。研究目標為於細胞實驗中測試硼酸對細胞之毒性、細胞積聚硼之能力與BNCT後之存活率，並以動物實驗評估BNCT治療之效果和輻射生物效應。
細胞實驗中使用大鼠骨肉瘤細胞(UMR-106)與老鼠結締組織細胞(L929)，測試其攝取硼藥物之能力與藥物之細胞毒性。結果顯示硼酸對L929細胞之細胞毒性較UMR-106細胞為高，以骨誘導基培養之UMR-106細胞比L929細胞能積聚更多硼原子。假設γ-ray之RBE值為1，以達成UMR-106細胞存活率為10%時，做評估基準，計算出中子照射之RBE為4.42，以硼酸為含硼藥物進行中子照射所得CBE值為5.53。
動物實驗中以UMR-106細胞接種於SD大鼠股骨已成功建立骨肉瘤動物模式，由硼酸於荷瘤大鼠之藥物動力學及生物分布之評估數據，決定大鼠於硼酸水溶液靜脈注射後1小時開始接受中子照射，腫瘤之處方劑量為5.8及11.0 Gy。藉由放射學影像確認腫瘤之大小，並以此評估骨組織之反應，另以體重變化監測動物體之生理狀況。結果顯示，大鼠經硼酸水溶液施藥後進行中子照射後之第5天，經BNCT治療者與未經治療者之腫瘤面積即有明顯的差異，於照射完80天後腫瘤之大小減少約90％，經病理切片檢查發現其殘留物之結痂物為類骨質與纖維結締組織，其中已無腫瘤細胞存在。BNCT照射後5天之輻射傷害觀察，顯示部分腫瘤鄰近組織有骨髓抑制之現象，但於照射後30天可見部分恢復，照射後80天之骨髓已與正常骨髓相似，唯睪丸之曲精小管及其細胞之萎縮於BNCT後之第80天尚未恢復。本研究證實硼酸水溶液可做為硼中子捕獲治療之含硼藥物，可有效治療骨肉瘤。

[1] E.N. Marieb, L.S. Kollett, P.Z. Zao, and T. Stabler, Human anatomy & physiology laboratory manual, San Francisco: Benjamin Cummings, 2001.
[2] V.J. Vigorita, B. Ghelman, and D. Mintz, Orthopaedic Pathology, Philadelphia: Lippincott Williams & Wilkins, 2007.
[3] H. Yabe and H. Hanaoka, “Investigation of the Origin of the Osteoclast by Use of Transplantation on Chick Chorioallantoic Membrane,” Clin Orthop Relat Res, (no. 197), pp. 255-265, 1985.
[4] W.M. Haschek and C.G. Rousseaux, Handbook of toxicologic pathology, San Diego: Academic Press, 1991.
[5] P. Picci, “Osteosarcoma (osteogenic sarcoma),” Orphanet J Rare Dis, vol. 2-6, pp. 6, 2007.
[6] 中華民國兒童癌症基金會, “骨癌的種類,” http://www.ccfroc.org.tw/child/child_affection_read.php?a_id=162007.
[7] M.J. Klein and G.P. Siegal, “Osteosarcoma: anatomic and histologic variants,” Am J Clin Pathol, vol. 125, (no. 4), pp. 555-481, Apr 2006.
[8] M. Kansara and D.M. Thomas, “Molecular pathogenesis of osteosarcoma,” DNA Cell Biol, vol. 26, (no. 1), pp. 1-18, 2007.
[9] W.S. Ferguson and A.M. Goorin, “Current Treatment of Osteosarcoma,” Cancer Invest, vol. 19, (no. 3), pp. 292-315, 2001.
[10] C.A. Stiller, S.S. Bielack, G. Jundt, and E. Steliarova-Foucher, “Bone tumours in European children and adolescents,1978–1997. Report from the Automated Childhood Cancer Information System project,” Eur J Cancer, vol. 42, pp. 2124-2135, 2006.
[11] H.T. Ta, C.R. Dass, P.F. Choong, and D.E. Dunstan, “Osteosarcoma treatment: state of the art,” Cancer Metast Rev vol. 28, (no. 1-2), pp. 247-263, 2009.
[12] T.J. Martin, P. MIngleton., J.C.E. Underwood, V.P. Michelangeli, N.H. Hunt, and R.A. Melick, “Parathyoid hormone-reponsive adenylate cyclase in induced transplantable osteogenic rat sarcoma,” Nature, vol. 260, (no. 5550), pp. 436-438, 1976.
[13] P.F.M. Choong, E.T.H. Ek, and C.R. Dass, “Commonly used mouse models of osteosarcoma,” Crit Rev Oncol Hematol, vol. 60, (no. 1), pp. 1-8, 2006.
[14] M.J. Coelho and M.H. Fernandes, “Human bone cell cultures in biocompatibility testing. Part II: effect of ascorbic acid, beta-glycerophosphate and dexamethasone on osteoblastic differentiation,” Biomaterials vol. 21, pp. 1095-1102, 2000.
[15] C.G. Bellows, J.N. Heersche, and J.E. Aubin, “Inorganic phosphate added exogenously or released from beta-glycerophosphate initiates mineralization of osteoid nodules in vitro,” Bone Miner, vol. 17, (no. 1), pp. 15-29, 1992.
[16] B. Cherrier, F. Gouin, M.F. Heymann, J.P. Thiery, F. Redini, D. Heymann, and F. Duteille, “A new experimental rat model of osteosarcoma established by intrafemoral tumor cell inoculation, useful for biology and therapy investigations,” Tumour Biol, vol. 26, (no. 3), pp. 121-130, 2005.
[17] L.M. Cobb, “Radiation-induced osteosarcoma in the rat as a model for osteosarcoma in man,” Br J Cancer, vol. 24, (no. 2), pp. 294-299, 1970.
[18] O. Berlin, D. Samid, R. Donthineni-Rao, W. Akeson, D. Amiel, and V.L. Woods, Jr., “Development of a novel spontaneous metastasis model of human osteosarcoma transplanted orthotopically into bone of athymic mice,” Cancer Res, vol. 53, (no. 20), pp. 4890-4895, 1993.
[19] J.L. Fisher, P.S. Mackie, M.L. Howard, H. Zhou, and P.F. Choong, “The expression of the urokinase plasminogen activator system in metastatic murine osteosarcoma: an in vivo mouse model,” Clin Cancer Res, vol. 7, pp. 1654-1660, 2001.
[20] Z. Yu, H. Sun, Q. Fan, H. Long, T. Yang, and B. Ma, “Establishment of reproducible osteosarcoma rat model using orthotopic implantation technique,” Oncol Rep, vol. 21, pp. 1175-1180, 2009.
[21] C. Ferrari, C. Zonta, L. Cansolino, A.M. Clerici, A. Gaspari, S. Altieri, S. Bortolussi, S. Stella, P. Bruschi, P. Dionigi, and A. Zonta, “Selective uptake of p-boronophenylalanine by osteosarcoma cells for boron neutron capture therapy,” Appl Radiat Isot, vol. 67, (no. 7-8 Suppl), pp. S341-344, 2009.
[22] D. Gabel, S. Foster, and R.G. Fairchild, “The Monte Carlo simulation of the biological effect of the 10B(n, alpha)7Li reaction in cells and tissue and its implication for boron neutron capture therapy,” Radiat Res, vol. 111, pp. 14-25, 1987.
[23] T.U. Probst, “Methods for boron analysis in boron neutron capture therapy (BNCT). A review,” Fresenius J Anal Chem, vol. 364, (no. 5), pp. 391-403, 1999.
[24] J.A. Coderre and G.M. Morris, “The radiation biology of boron neutron capture therapy,” Radiat Res, vol. 151, (no. 1), pp. 1-18, 1999.
[25] R.F. Barth, J.A. Coderre, M.G.H. Vicente, and B. T.E., “Boron neutron capture therapy of cancer: current status and future prospects.,” Clin. Cancer Res, vol. 11, pp. 3987-4002, 2005.
[26] J.A. Coderre, J.D. Glass, S. Packer, P. Micca, and D. Greenberg, “Experimental boron neutron capture therapy for melanoma: systemic delivery of boron to melanotic and amelanotic melanoma,” Pigment Cell Res, vol. 3, (no. 6), pp. 310-318, 1990.
[27] A. Wittig, W.A. Sauerwein, and J.A. Coderre, “Mechanisms of transport of p-borono-phenylalanine through the cell membrane in vitro,” Radiat Res, vol. 153, (no. 2), pp. 173-180, Feb 2000.
[28] G.M. Morris, J.A. Coderre, J.W. Hopewell, P.L. Micca, M.M. Nawcocky, H.B. Liu, and A. Bywaters, “Response of the central nervous system to boron neutron capture irradiation: Evaluation using rat spinal cord model. ,” Radiother Oncol, vol. 32, pp. 249-255, 1994.
[29] J.T. Goodwin, L.E. Farr, W.H. Sweet, and J.S. Robertson, “Pathological study of eight patients with glioblastoma multiforme treated by neutron-capture therapy using boron 10,” Cancer, vol. 8, (no. 3), pp. 601-615, 1955.
[30] L.E. Farr, W.H. Sweet, J.S. Robertson, C.G. Foster, H.B. Locksley, D.L. Sutherland, M.L. Mendelsohn, and E.E. Stickley, “Neutron capture therapy with boron in the treatment of glioblastoma multiforme,” Am J Roentgenol Radium Ther Nucl Med, vol. 71, (no. 2), pp. 279-293, 1954.
[31] F.J. Murray, “A comparative review of the pharmacoketics of boric acid in rodents and humans,” Biol Trace Elem Res, vol. 66, pp. 331-341, 1998.
[32] T.A. Devirian and S.L. Volpe, “The physiological effects of dietary boron,” Crit Rev Food Sci Nutr, vol. 43, (no. 2), pp. 219-231, 2003.
[33] A.S. See, A.B. Salleh, F.A. Bakar, N.A. Yusof, A.S. Abdulamir, and L.Y. Heng, “Risk and health effects of boric acid,” Am J Applied Sci, vol. 7, (no. 5), pp. 620-627, 2010.
[34] J.A. Jansen, J. Andersen, and J.S. Schou, “Boric aicd single dose pharmacokinetics after intravenous administration to man,” Arch Toxicol, vol. 55, pp. 64-67, 1984.
[35] M. Dahlstrom, J. Capala, P. Lindstrom, A. Wasteson, and A. Lindstrom, “Accumulation of boron in human malignant glioma cells in vitro is cell type dependent,” J Neurooncol, vol. 68, (no. 3), pp. 199-205, Jul 2004.
[36] E.M. Heber, V.A. Trivillin, D. Nigg, E.L. Kreimann, M.E. Itoiz, R.l.J. Rebagliati, D. Batistoni, and A.E. Schwint, “Biodistribution of GB-10(Na210B10H10) compound for boron neutron capture therapy (BNCT) in an experimental model of oral in the hamster cheek pouch,” Arch Oral Biol, vol. 49, pp. 313-324, 2004.
[37] E.M. Heber, V.A. Trivillin, D.W. Nigg, M.E. Itoiz, B.N. Gonzalez, R.l.J. Rebagliati, D. Batistoni, E.L. Kreimann, and A.E. Schwint, “Homogeneous boron targeting of heterogeneous tumors for boron neutron capture therapy (BNCT):Chemical analyses in the hamster cheek pouch oral cancer model,” Arch Oral Biol, vol. 51, pp. 922-929, 2006.
[38] D.H. Kim, K.F. Faull, A.J. Norris, and C.D. Eckhert, “Borate-nucleotide complex formation depends on charge and phosphorylation state,” J Mass Spectrom, vol. 39, (no. 7), pp. 743-751, 2004.
[39] C.D. Hunt, “Regulation of enzymatic activity one possible role of dietary boron in higher animals and humans ” Biol Trace Elem Res, vol. 66, pp. 205-225, 1998.
[40] C. Eckhert, W. Barranco, and D. Kim, “Boron and prostate cancer a model for understanding boron biology,” in Proc. Advances in Plant and Animal Boron Nutrition, 2007, pp. Pages.
[41] J. Deacon, M.J. Peckham, and G.G. Steel, “The radioresponsiveness of human tumours and the initial slope of the cell survival curve,” Radiother Oncol, vol. 2, (no. 4), pp. 317-323, 1984.
[42] S. Tatezaki, “Systematic multi-modal treatment of osteosarcoma, with special reference to the role of fast neutron radiotherapy,” J Jap Orthop Ass, vol. 53, pp. 831-846, 1970.
[43] T. Kadosawa, F. Ohashi, R. Nishimura, N. Sasaki, I. Saito, H. Wakabayashi, and A. Takeuchi, “Relative biological effectiveness and tolerance dose of fission neutrons in canine skin for a potential combination of neutron capture therapy and fast-neutron therapy,” Radiat Res, vol. 160, (no. 4), pp. 436-442, 2003.
[44] A. Takeuchi, “Possible application of boron neutron capture therapy to canine osteosarcoma,” Nippon Juigaku Zasshi, vol. 47, (no. 6), pp. 869-878, 1985.
[45] R.G. Zamenhof, “Microdosimetry for boron neutron capture therapy: A review,” J Neurooncol, vol. 33, (no. 1-2), pp. 81-92, 1997.
[46] J.A. Coderre, M.S. Makar, P.L. Micca, M.M. Nawrocky, H.B. Liu, D.D. Joel, D.N. Slatkin, and H.I. Amols, “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,” Int J Radiat Oncol Biol Phys, vol. 27, (no. 5), pp. 1121-1129, 1993.
[47] W.S. Kiger, 3rd, X.Q. Lu, O.K. Harling, K.J. Riley, P.J. Binns, J. Kaplan, H. Patel, R.G. Zamenhof, Y. Shibata, I.D. Kaplan, P.M. Busse, and M.R. Palmer, “Preliminary treatment planning and dosimetry for a clinical trial of neutron capture therapy using a fission converter epithermal neutron beam,” Appl Radiat Isot, vol. 61, (no. 5), pp. 1075-1081, 2004.
[48] S. Kawabata, S. Miyatake, T. Kuroiwa, K. Yokoyama, A. Doi, K. Iida, S. Miyata, N. Nonoguchi, H. Michiue, M. Takahashi, T. Inomata, Y. Imahori, M. Kirihata, Y. Sakurai, A. Maruhashi, H. Kumada, and K. Ono, “Boron neutron capture therapy for newly diagnosed glioblastoma,” J Radiat Res (Tokyo), vol. 50, (no. 1), pp. 51-60, 2009.
[49] M. Suzuki, S.I. Masunaga, Y. Kinashi, M. Takagaki, Y. Sakurai, T. Kobayashi, and K. Ono, “The effects of boron neutron capture therapy on liver tumors and normal hepatocytes in mice,” Jpn J Cancer Res, vol. 91, (no. 10), pp. 1058-1064, 2000.
[50] M. Suzuki, Y. Sakurai, S. Masunaga, Y. Kinashi, K. Nagata, and K. Ono, “Dosimetric study of boron neutron capture therapy with borocaptate sodium (BSH)/lipiodol emulsion (BSH/lipiodol-BNCT) for treatment of multiple liver tumors,” Int J Radiat Oncol Biol Phys, vol. 58, (no. 3), pp. 892-896, 2004.
[51] M.A. Dagrosa, M. Crivello, M. Perona, S. Thorp, G.A. Santa Cruz, E. Pozzi, M. Casal, L. Thomasz, R. Cabrini, S. Kahl, G.J. Juvenal, and M.A. Pisarev, “First evaluation of the biologic effectiveness factors of boron neutron capture therapy (BNCT) in a human colon carcinoma cell line,” Int J Radiat Oncol Biol Phys, vol. 79, (no. 1), pp. 262-268, 2011.
[52] J.L. Kiger, W. S. III Kiger, K.J. Riley, P.J. Binns, H. Patel, J.W. Hopewell, O.K. Harling, P.M. Busse, and J.A. Coderre, “Functional and histological changes in rat lung after boron neutron capture therapy,” Radiat Res vol. 170, pp. 60-69, 2008.
[53] J. Gueulette, H.M. Liu, S.H. Jiang, Y.W.H. Liu, B.M.D. Coster, Y.H. Liu, W. C.Tsai, A. Wambersie, and A.Y. Chen, “Radiobiological Characterization of the Epithermal Neutron Beam Produced at the Tsing Hua Open-Pool Reactor (THOR) for BNCT: Comparison with Other BNCT Facilities,” Therapeut Radiol Oncol, vol. 13, (no. 2), pp. 135-146, 2006.
[54] M.J. Cornelissen, H.A. Declerq, R.M.H. Verbeeck, L.I.F.J.M. De Ridder, and E.H. Schacht, “Calcification as an indicator of osteoinductive capacity of biomaterials in osteoblastic cell cultures,” Biomaterials, vol. 26, (no. 24), pp. 4964-4974, 2005.
[55] P. Armitage and I. Allen, “Methods of estimating the LD 50 in quantal response data,” J Hyg (Lond), vol. 48, (no. 3), pp. 298-322, 1950.
[56] C.D. Sibrack, L.T. Gutman, C.M. Wilfert, C. McLaren, M.H. St Clair, P.M. Keller, and D.W. Barry, “Pathogenicity of acyclovir-resistant herpes simplex virus type 1 from an immunodeficient child,” J Infect Dis, vol. 146, (no. 5), pp. 673-82, Nov 1982.
[57] D.J. Pizzarello, Radiation biology, Boca Raton, Fla.: CRC Press, 1982.
[58] E.J. Hall and A.J. Giaccia, Radiobiology for the radiologist, Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2012.
[59] Y.H. Liu, P.E. Tsai, H.M. Liu, and S.H. Jiang, “Characterization of a BNCT beam using neutron activation and indirect neutron radiography,” Radiat Meas, vol. 45, (no. 10), pp. 1167-1170, 2010.
[60] K.L. Weber, M. Doucet, J.E. Price, C. Baker, S.J. Kim, and I.J. Fidler, “Blockade of epidermal growth factor receptor signaling leads to inhibition of renal cell carcinoma growth in the bone of nude mice,” Cancer Res, vol. 63, (no. 11), pp. 2940-2947, 2003.
[61] M. Goblirsch, W. Mathews, C. Lynch, P. Alaei, B.J. Gerbi, P.W. Mantyh, and D.R. Clohisy, “Radiation treatment decreases bone cancer pain, osteolysis and tumor size,” Radiat Res, vol. 161, (no. 2), pp. 228-234, 2004.
[62] M. Goblirsch, C. Lynch, W. Mathews, J.C. Manivel, P.W. Mantyh, and D.R. Clohisy, “Radiation treatment decreases bone cancer pain through direct effect on tumor cells,” Radiat Res, vol. 164, pp. 400-408, 2005.
[63] C.P. Reynolds, B.C. Sun, Y.A. DeClerck, and R.A. Moats, “Assessing growth and response to therapy in murine tumor models,” Methods Mol Med, vol. 111, pp. 335-350, 2005.
[64] M. Ying, S. Wang, Y. Sang, P. Sun, B. Lal, C.R. Goodwin, H. Guerrero-Cazares, A. Quinones-Hinojosa, J. Laterra, and S. Xia, “Regulation of glioblastoma stem cells by retinoic acid: role for Notch pathway inhibition,” Oncogene, vol. 30, (no. 31), pp. 3454-3467, Aug 2011.
[65] S. Morony, C. Capparelli, I. Sarosi, D.L. Lacey, C.R. Dunstan, and P.J. Kostenuik, “Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis,” Cancer Res, vol. 61, (no. 11), pp. 4432-6, Jun 1 2001.
[66] S. Levin, T.J. Bucci, S.M. Cohen, A.S. Fix, J.F. Hardisty, E.K. LeGrand, R.R. Maronpot, and B.F. Trump, “The nomenclature of cell death: recommendations of an ad hoc Committee of the Society of Toxicologic Pathologists,” Toxicol Pathol, vol. 27, (no. 4), pp. 484-490, 1999.
[67] W. Small and G.E. Woloschak, Radiation toxicity : a practical guide, New York: Springer, 2006.
[68] P.S. Walmod, U. Gravemann, H. Nau, V. Berezin, and E. Bock, “Discriminative power of an assay for automated in vitro screening of teratogens,” Toxicol In Vitro, vol. 18, (no. 4), pp. 511-525, 2004.
[69] N.D. Vaziri, F. Oveisi, B.D. Culver, M.V. Pahl, M.E. Andersen, P.L. Strong, and F.J. Murray, “The effect of pregnancy on renal clearance of boron in rats given boric acid orally,” Toxicol Sci, vol. 60, (no. 2), pp. 257-263, 2001.
[70] H. Fukuda, M. Ichihashi, T. Kobayashi, D. Matsuzawa, K. Kanda, and Y. Mishima, “Review: biological effectiveness of thermal neutrons and 10B(n,alpha)7Li reaction on cultured cells,” Pigment Cell Res, vol. 2, pp. 333-336, 1989.
[71] H. Fukuda, T. Kobayashi, T. Matsuzawa, K. Kanda, M. Ichihashi, and Y. Mishima, “RBE of a thermal neutron beam and the 10B(n, alpha)7Li reaction on cultured B-16 melanoma cells,” Int J Radiat Biol Relat Stud Phys Chem Med, vol. 51, pp. 167-175, 1987.
[72] M.A. Davis, J.B. Little, K.M. Ayyangar, and A.R. Reddy, “Relative biological effectiveness of the 10B(n, alpha)7 Li reaction in HeLa cells,” Radiat Res, vol. 43, (no. 3), pp. 534-553, 1970.
[73] D. Gabel, R.G. Fairchild, B. Larsson, and H.G. Borner, “The relative biological effectiveness in V79 Chinese hamster cells of the neutron capture reactions in boron and nitrogen,” Radiat Res, vol. 98, pp. 307-316, 1984.
[74] X. Hao and Q. Fan, “Establishment and preliminary evaluation of rat animal model bearing a transplantable osteosarcoma,” Chin J Comp Med, vol. 14, (no. 6), pp. 229-331, 2004.
[75] T.J. Rosol, S.H. Tannehill-Gregg, S. Corn, A. Schneider, and L.K. McCauley, “Animal models of bone metastasis,” Cancer Treat Res, vol. 118, pp. 47-81, 2004.
[76] F. Blanchard, B. Brounais, C. Chipoy, K. Mori, C. Charrier, S. Battaglia, P. Pilet, C.D. Richards, D. Heymann, and F. Redini, “Oncostatin M induces bone loss and sensitizes rat osteosarcoma to the antitumor effect of midostaurin in vivo,” Clin Cancer Res, vol. 14, (no. 17), pp. 5400-5409, 2008.
[77] F. Redini, F. Lamoureux, G. Picarda, J. Rousseau, C. Gourden, S. Battaglia, C. Charrier, B. Pitard, and D. Heymann, “Therapeutic efficacy of soluble receptor activator of nuclear factor-kappa B-Fc delivered by nonviral gene transfer in a mouse model of osteolytic osteosarcoma,” Mol Cancer Ther, vol. 7, (no. 10), pp. 3389-3398, 2008.
[78] J. Yuan, C. Ossendorf, J.P. Szatkowski, J.T. Bronk, A. Maran, M. Yaszemski, M.E. Bolander, G. Sarkar, and B. Fuchs, “Osteoblastic and osteolytic human osteosarcomas can be studied with a new xenograft mouse model producing spontaneous metastases,” Cancer Invest, vol. 27, (no. 4), pp. 435-442, 2009.
[79] J.P. Farese, A.R. Coomer, R. Milner, D. Taylor, M.E. Salute, D.A. Rajon, F.J. Bova, and D.W. Siemann, “Development of an intramuscular xenograft model of canine osteosarcoma in mice for evaluation of the effects of radiation therapy,” Am J Vet Res, vol. 70, (no. 1), pp. 127-133, 2009.
[80] C. Khanna, J. Prehn, C. Yeung, J. Caylor, M. Tsokos, and L. Helman, “An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential,” Clin Exp Metastasis, vol. 18, (no. 3), pp. 261-271, 2000.
[81] G.J. Bakeine, M. Di Salvo, S. Bortolussi, S. Stella, P. Bruschi, A. Bertolotti, R. Nano, A. Clerici, C. Ferrari, C. Zonta, A. Marchetti, and S. Altieri, “Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases,” Appl Radiat Isot, vol. 67, (no. 7-8 Suppl), pp. S332-335, 2009.
[82] J.L. Kiger, W.S. Kiger, H. Patel, P.J. Binns, K.J. Riley, J.W. Hopewell, O.K. Harling, and J.A. Coderre, “Effects of boron neutron capture irradiation on the normal lung of rats,” Appl Radiat Isot, vol. 61, (no. 5), pp. 969-973, 2004.
[83] R. Dennis, Handbook of small animal radiology and ultrasound : techniques and differential diagnoses, Edinburgh ; New York: Churchill Livingstone/Elsevier, 2010.
[84] J.W. Hopewell, “Radiation-therapy effects on bone density,” Med Pediatr Oncol, vol. 41, (no. 3), pp. 208-211, 2003.
[85] P.G. Bullough, Orthopaedic pathology, Philadelphia: Mosby, 2004.
[86] D.E. Thrall, Textbook of veterinary diagnostic radiology, philadelphia: Elsevier, 2002.
[87] D.H. Percy and S.W. Barthold, Pathology of laboratory rodents and rabbits, Ames, Iowa: Blackwell Pub., 2007.
[88] M. Sugimoto, S. Takahashi, J. Toguchida, Y. Kotoura, Y. Shibamoto, and T. Yamamuro, “Changes in bone after high-dose irradiation. Biomechanics and histomorphology,” J Bone Joint Surg Br, vol. 73, (no. 3), pp. 492-497, 1991.
[89] S. Takahashi, M. Sugimoto, Y. Kotoura, K. Sasai, M. Oka, and T. Yamamuro, “Long-term changes in the haversian systems following high-dose irradiation. An ultrastructural and quantitative histomorphological study,” J Bone Joint Surg Am, vol. 76, (no. 5), pp. 722-738, 1994.
[90] I. Kato, K. Ono, Y. Sakurai, M. Ohmae, A. Maruhashi, Y. Imahori, M. Kirihata, M. Nakazawa, and Y. Yura, “Effectiveness of BNCT for recurrent head and neck malignancies,” Appl Radiat Isot, vol. 61, (no. 5), pp. 1069-1073, 2004.