最佳化Boronophenylalanine為含硼藥物之硼中子捕獲治療-以小鼠口腔癌模式進行臨床前研究

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研究生：	林佑娟 Lin, Yu Chuan
論文名稱：	最佳化Boronophenylalanine為含硼藥物之硼中子捕獲治療-以小鼠口腔癌模式進行臨床前研究 An optimized boronophenylalanine-mediated BNCT treatment– preclinical studies using an oral squamous carcinoma cell murine xenograft model
指導教授：	周鳳英 Chou, Fong In 梁正宏 Liang Jenq Horng
口試委員:	高志浩李易展黃正仲王世楨顏上惠
學位類別：	博士 Doctor
系所名稱：	原子科學院 - 核子工程與科學研究所 Nuclear Engineering and Science
論文出版年：	2016
畢業學年度：	104
語文別：	英文
論文頁數：	114
中文關鍵詞：	硼中子補獲治療、低劑量加馬輻射、藥物動力學、F-18 BPA 正子照影、硼藥物微分佈、頭頸部腫瘤
外文關鍵詞：	Boron neutron capture therapy (BNCT), Low dose gamma radiation (LDR), Pharmacokinetics, F-18 BPA PET, Boron drug micro-distribution, Head and neck cancer
相關次數：	點閱：2 下載：0
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根據衛生福利部2013年之統計資料顯示口腔癌為十大癌症死因之第5位，口腔癌不僅治療後有高的復發率，而且轉移到頸部淋巴結之機率高，一旦轉移至淋巴結治療之預後極差，因此頸部淋巴結轉移為口腔癌預後之指標。硼中子捕獲治療(Boron neutron capture therapy；BNCT)是治療癌病之新利器，利用硼藥物會選擇性大量積聚於腫瘤組織中，而正常組織之積聚量少之特性，給予腫瘤照射熱中子，熱中子會與腫瘤組織中之硼藥物發生核反應產生α粒子及7Li，兩種粒子皆為高線性能量轉移之粒子，在約一個細胞之距離內將能量完全釋放而達到殺死腫瘤細胞的目的，並降低正常組織之傷害。BNCT之成功要素為高的腫瘤硼濃度、高的腫瘤與正常組織之硼濃度比值、硼積聚於腫瘤組織中之分佈均勻度及高品質之中子射束。本研究是以Boronophenylalanine (BPA)為硼藥物進行評估硼中子捕獲治療口腔癌之相關研究，研究進行分為四個子題，子題一(a)：利用低劑量之加馬輻射增加頭頸部腫瘤中之硼濃度，子題一(b)：以低劑量之加馬射線增加原位口腔癌動物模式之腫瘤硼濃度並提高BNCT治療效果，子題二：探討以18F-BPA正子攝影與ICP-AES分析BPA之藥物動力學及其硼濃度比值間的相關性，子題三：探討BPA於腫瘤中之巨觀及微觀分佈均勻度，子題四：探討最佳之施藥方式以維持腫瘤中之硼濃度及縮小正常組織與血液硼濃度之比值。

According to the Ministry of Health and Welfare, oral cancer was the fifth most common throughout the population in 2013. Oral cancer has a high recurrence rate and frequently metastasizes to cervical lymph nodes. Lymph node metastasis has a poor prognosis and is a prognostic index for oral cancer. Boron neutron capture therapy (BNCT) is a promising new modality for cancer treatment. In BNCT, boronophenylalanine (BPA) accumulates in a tumor, while being present at a much lower level in a normal tissue. After boron drug treatment, the tumor is irradiated with thermal neutron inducing α-particles and 7Li. These two particles have a high linear energy transfer. All of their energy is deposited in cells, effectively killing tumor cells while doing little damage to normal tissue. The therapeutic success of BNCT depends on the high boron concentration in the tumor, the high tumor-to-the normal tissue boron ratio, the homogenous distribution of boron in the tumor and the high-quality thermal neutron beam. Therefore, this involves a series of investigations to evaluate the therapeutic effect of BPA-mediated BNCT against oral cancer. The program has four parts. In Part I.a, low dose of gamma irradiation enhances boronophenylalanine uptake in head and neck carcinoma cells for boron neutron capture therapy. In Part I.b, the boron concentration is increased in the tumor using low-dose gamma radiation to improve the therapeutic efficiency of BPA-mediated BNCT in an orthotopic oral cancer animal model. In Part II, the pharmacokinetics and tumor to normal tissue boron ratios are obtained by 18F-BPA-PET scan before BNCT and that obtained by ICP-AES analysis following real-time BNCT treatment in an orthotopic oral cancer model. In Part III, macro- and micro-distributions of BPA are analyzed in a subcutaneous xenograft model for BNCT. In Part IV, the administration of BPA is optimized to maintain a high boron concentration in tumor and narrow down the range of normal tissue to blood boron ratios in BNCT in a mouse model.

目錄
摘要…………………………………………………………………………………………….1
Abstract………………………………………………………………………………………..2
Part I.a: Low dose of gamma irradiation enhanced boronophenylalanine uptake in head and neck carcinoma cells for boron neutron capture therapy    4
Abstract………………………………………………………………………………………..4
1a.1 Introduction    5
1a.2 Materials and Methods    6
1a.2.1 Cell culture    6
1a.2.2 Preparation of boronophenylalanine (BPA) solution    7
1a.2.3 Cytotoxicity analysis by sulforhodamine B (SRB) staining    7
1a.2.4 Cell cycle analysis using flow cytometry    8
1a.2.5 Boron concentration analysis for SAS cells by inductively coupled plasma with atomic emission spectroscopy (ICP-AES)    8
1a.2.6 The experimental design of increasing boron concentration for SAS cells    9
1a.2.7 Low dose γ-ray irradiation for SAS cells    11
1a.2.8 Neutron irradiation for cells    11
1a.2.9 Clonogenic assay    12
1a.2.10 Cell morphology analysis    13
1a.2.11 Statistical analysis    13
1a.3 Results…………………………………………………………………………………..13
1a.3.1 Cytotoxicity of BPA for SAS cells    13
1a.3.2 Boron uptake of SAS cells    14
1a.3.3 Surviving fraction of BNCT SAS cells    17
1a.3.4 Distribution and morphology of SAS cells after neutron irradiation    18
1a.3.5 G2/M cell cycle arrest of BNCT-treated SAS cells    20
1a.4 Conclusions    21
Part I.b: Increasing the boron concentration in the tumor using low-dose gamma radiation to improve the therapeutic efficiency of BPA-mediated BNCT in an orthotopic oral cancer animal model    22
Abstract………………………………………………………………………………………22
1b.1 Introduction    24
1b.2 Materials and Methods    27
1b.2.1 Cell culture    27
1b.2.2 Preparation of boronophenylalanine (BPA) solution    28
1b.2.3 Orthotopic mouse model of tongue cancer    28
1b.2.4 Biodistribution studies of boronophenylalnine (BPA)    29
1b.2.5 Boron concentration analysis for organs by inductively coupled plasma with atomic emission spectroscopy (ICP-AES)    29
1b.2.6 The experimental design for increasing boron concentration in the tumor in orthotopic animal model    30
1b.2.7 Low dose γ-rays irradiation for animal    32
1b.2.8 Neutron irradiation for animals    32
1b.2.9 Preparing 18F-Fluoro-L-Boronophenylalanine Fructose (18F-BPA)    36
1b.2.10 Micro-computer tomography (micro-CT) and micro-positron emission tomography (micro-PET) images    36
1b.2.11 Therapeutic effect evaluation following treatment by bioluminescence image (BLI), monitored body weight and pathology analyses    39
1b.2.12 Statistical analysis    40
1b.3 Results…………………………………………………………………………………..40
1b.3.1 LDR improved BPA accumulation in a tumor in an orthotopic oral cancer model    40
1b.3.2 The enhancement of radiation dose by LDR in combination treatment group    42
1b.3.3 The negative correlation between relative photon flux (RPF) and body weight    45
1b.3.4 LDR potential enhancement of therapeutic effect for with or without metastases in bearing-tumor mice    47
1b.3.5 The complete response for the primary and secondary tumors (metastasis) using pathology analysis after treatment in combined treatment group    50
1b.4 Discussion and Conclusions    55
Part II: The pharmacokinetics and tumor to normal tissue boron ratios obtained by 18F-BPA-PET scan before BNCT and that obtained by ICP-AES analysis following real-time BNCT treatment in an orthotopic oral cancer model    60
Abstract………………………………………………………………………………………60
2.1 Introduction    62
2.2 Materials and Methods    63
2.2.1 Human oral squamous cells carcinoma SAS cells culture    63
2.2.2 Preparing boronophenylalanine (BPA) solution    64
2.2.3 Orthotopic SAS cell-bearing model    64
2.2.4 Bioluminescence image (BLI) monitoring tumor growth    65
2.2.5 18F-Fluoro-L-Boronophenylalanine Fructose (18F-BPA) labelling    65
2.2.6 18F-BPA biodistribution analysis using dynamic micro-positron emission tomography    66
2.2.7 Biodistribution of BPA for the mice by ICP-AES analysis    67
2.3 Results……………………………………………………………………………………68
2.3.1 Biodistribution of BPA analysis using ICP-AES in orthotropic animal model    68
2.3.2 Pharmacokinetic of 18F-BPA using micro-PET analysis    69
2.3.3 The T/N, the T/B and the N/B ratios correlation between BPA and 18F-BPA    74
2.4 Discussion and Conclusions    76
Part III: Macro- and micro-distributions of BPA in a subcutaneous xenograft model for BNCT…………………………………………………………………………...……………79
Abstract………………………………………………………………………………………79
3.1 Introduction    81
3.2 Material and Methods    83
3.2.1 Human cell squmous cell carcinoma SAS cell culture.    83
3.2.2 Preparation of BPA-fructose solution    83
3.2.3 Subcutaneous xenograft model and BPA administration    84
3.2.4 Boron concentration analysis by ICP-AES    84
3.2.5 Preparation of 18F-fluoro-L-boronophenylalanine fructose (18F-BPA)    85
3.2.6 Dynamic micro-positron-emission tomographic (micro-PET) imaging and analysis    86
3.2.7 Autoradiographic analysis of microdistribution of boron in tumor    87
3.2.8 Statistical analysis    87
3.3 Results……………………………………………………………………………………88
3.3.1 Biodistribution of BPA in tumor-bearing mice    88
3.3.2 Boron concentrations and boron ratios    89
3.3.3 Distribution of 18F-BPA in tumor    91
3.3.4 Distribution of boron-10 in tumor    93
3.4 Discussion and Conclusions    95
Part IV: Optimizing administration of BPA to maintain a high boron concentration in tumor and narrow down the range of normal tissue to blood boron ratios in BNCT in a mouse model…………………………………………………………………………………98
Abstract………………………………………………………………………………………98
4.1 Introduction    100
4.2 Material and Methods    103
4.2.1 Cell culture for human oral squamous cell carcinoma SAS cells    103
4.2.2 SAS human oral squamous carcinoma cells on a tumor-bearing mice model    103
4.2.3 The experiment design for the pharmacokinetics in blood and the biodistritusion analyses    104
4.2.4 Boron concentration analysis by ICP-AES    105
4.3 Results…………………………………………………………………………………..106
4.3.1 Biodistribution of BPA in SAS cells xenograft-bearing mice    106
4.3.2 Enhancing the T/N and the T/B ratios in the two steps infusion group    110
4.3.3 A high accurate prediction of boron concentration in the two-step group than in the one-step infusion group    111
4.4 Discussion and Conclusions    113
References    116

表目錄
Table 1. The boron concentration ratios obtained from biodistribution analysis in mice bearing orthotopic human oral squamous cell carcinoma in neutron alone, BNCT and combination treatment groups    35
Table 2. Relative biological effectiveness (RBE)-dose in the organs using Xplan treatment planning……………………………………………………………………………………….35
Table 3. The biodistribution in mice bearing orthotopic human oral squamous cell carcinoma in BPA and combination treatment groups    41
Table 4. The T/N, the T/B and the N/B ratios in BPA alone and combination treatment group in mice bearing orthotopic human oral squamous cell carcinoma    42
Table 5. The predicted boron concentration of the organs during neutron irradiation in orthotopic oral squamous cell carcinoma mice    44
Table 6. Radiation dose for neutron alone, BNCT and combination groups in orthotopic oral squamous cell carcinoma mice    45
Table 7. The T/N, the T/B and the N/B ratios relationships between BPA and 18F-BPA in orthotopic oral tumor-bearing mice    74
Table 8. The T/N, T/B and N/B boron concentration ratios in mice administrated boronophenylalanine (BPA)    91
Table 9. 18F-BPA activity in region of interest (ROI) of active and non-active tumor regions on transverse planes of mouse tumor    93
Table 10. The T/N, the T/B and the N/B boron ratios at 0, 15, 30, 45 and 60 min after the first step infusion in both the one-step and the two-step infusion groups    110
Table11. The boron concentration variation between measurement and prediction by percentage error analysis at 15, 30, 45 and 60 min after the first-step infusion in both the one-step and the two-step infusion groups    112

圖目錄
Figure 1. The scheme of experimental design for increasing boron concentration for SAS cells…………………………………………………………………………………………...10
Figure 2. Cells were irradiated with neutron radiation    12
Figure 3. Cytotoxicity analysis of boronophenylalanine (BPA) for SAS cells by sulforhodamine B (SRB) staining    14
Figure 4. Boron concentration analysis in SAS cells by ICP-AES    15
Figure 5. Boron concentrations in BPA combined low dose gamma irradiated SAS cells    16
Figure 6. Surviving fraction of the untreated, BPA treated, and BPA combined gamma irradiation treated SAS cells after neutron irradiation    17
Figure 7. Distribution and morphological changes of SAS cells after neutron irradiation    19
Figure 8. G2/M population of SAS cells after irradiating 5.46×1011 n/cm2 of neutron fluence and incubating for 24 hours    20
Figure 9. The scheme of experimental design for bearing-tumor mice with and without metastases for BNCT    31
Figure 10. The mice were irradiated with low dose γ-rays    32
Figure 11. Mice were placed in the whole radiation phantom and posited by laser line    34
Figure 12. Micro-CT and 18F-BPA micro-PET fusion image defined the tumor and the normal tissues for BNCT treatment planning    38
Figure 13. Monitoring the relative photon flux and the body weight change after treatment in orthotopic tongue squamous cell carcinoma animal model    46
Figure 14. The monitoring tumor growth using bioluminescence image (BLI) to evaluate therapeutic effect    49
Figure 15. Survival rate analysis by Kaplan-Meier method    50
Figure 16. The pathologies of the tongue and the lymph node for initial non-metastases mice after treatment………………………………………………………………………………...53
Figure 17. The pathologies of the tongue and the cervical lymph node for initial metastasis mice after treatment    54
Figure 18. Biodistribution of BPA in orthoropic tumor-bearing model    69
Figure 19. The pharmacokinetic of 18F-BPA using micro-PET in orthotopic tumor-bearing mice…………………………………………………………………………………………...70
Figure 20. Micro-PET section image of the tumor    71
Figure 21. Micro-PET section image of the muscle    71
Figure 22. Micro-PET section image of the heart blood pool    72
Figure 23. The pharmacokinetic of the tumor, the muscle and the blood relationships between BPA and 18F-BPA    73
Figure 24. The correlation between BPA and 18F-BPA for the T/N, the T/B and the N/B ratios using linear regression analysis    75
Figure 25. Boron concentration analysis by ICP-AES in subcutaneous xenograft model    89
Figure 26. Boron concentrations in tumor, muscle and blood by ICP-AES analysis    90
Figure 27. 18F-BPA distribution of tumor by micro-PET analysis    92
Figure 28. BPA microdistribution of tumor analysis by autoradiography    94
Figure 29. The BPA infusion protocol in SAS xenograft-bearing mice    105
Figure 30. Boron accumulation analysis in SAS xenograft-bearing mice    108
Figure 31. Biodistribution of BPA in SAS xenograft-bearing mice    109
Appendix Figure A1. Evaluation of radiation damage in salivary gland using pathology analysis in orthotopic tongue squamous cell carcinoma mice    131
Appendix Figure A2. Evaluation of radiation damage in liver using pathology analysis in orthotopic tongue squamous cell carcinoma mice    132
Appendix Figure A3. Evaluation of radiation damage in pancreas using pathology analysis in orthotopic tongue squamous cell carcinoma mice    133
Appendix Figure A4. Evaluation of radiation damage in kidney using pathology analysis in orthotopic tongue squamous cell carcinoma mice    134


                                

1. Kao SY, Chu YW, Chen YW, Chang KW, Liu TY. Detection and screening of oral cancer and pre-cancerous lesions. J Chin Med Assoc. 2009;72:227-33.
2. Chang MF, Wang HM, Kang CJ, Huang SF, Lin CY, Fang KH, et al. Treatment results for hypopharyngeal cancer by different treatment strategies and its secondary primary--an experience in Taiwan. Radiat Oncol. 2010;5:91.
3. Barth RF, Coderre JA, Vicente MG, Blue TE. Boron neutron capture therapy of cancer: current status and future prospects. Clin Cancer Res. 2005;11:3987-4002.
4. Coderre JA, Morris GM. The radiation biology of boron neutron capture therapy. Radiat Res. 1999;151:1-18.
5. Mehta SC, Lu DR. Targeted drug delivery for boron neutron capture therapy. Pharm Res. 1996;13:344-51.
6. Wittig A, Sauerwein WA, Coderre JA. Mechanisms of transport of p-borono-phenylalanine through the cell membrane in vitro. Radiat Res. 2000;153:173-80.
7. Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H. Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem. 1998;273:23629-32.
8. Anai S, Brown BD, Nakamura K, Goodison S, Hirao Y, Rosser CJ. Irradiation of human prostate cancer cells increases uptake of antisense oligodeoxynucleotide. Int J Radiat Oncol Biol Phys. 2007;68:1161-8.
9. Davies Cde L, Lundstrom LM, Frengen J, Eikenes L, Bruland SO, Kaalhus O, et al. Radiation improves the distribution and uptake of liposomal doxorubicin (caelyx) in human osteosarcoma xenografts. Cancer Res. 2004;64:547-53.
10. Zhang M, Li S, Li J, Ensminger WD, Lawrence TS. Ionizing radiation increases adenovirus uptake and improves transgene expression in intrahepatic colon cancer xenografts. Mol Ther. 2003;8:21-8.
11. Liu Y, Nagata K, Masunaga S, Suzuki M, Kashino G, Kinashi Y, et al. Gamma-ray irradiation enhanced boron-10 compound accumulation in murine tumors. Journal of radiation research. 2009;50:553-7.
12. Coderre JA, Chanana AD, Joel DD, Elowitz EH, Micca PL, Nawrocky MM, et al. Biodistribution of boronophenylalanine in patients with glioblastoma multiforme: boron concentration correlates with tumor cellularity. Radiat Res. 1998;149:163-70.
13. Lin YC, Hwang JJ, Wang SJ, Yang BH, Chang CW, Hsiao MC, et al. Macro- and microdistributions of boron drug for boron neutron capture therapy in an animal model. Anticancer Res. 2012;32:2657-64.
14. Lin YC, Wang SJ, Chung HP, Liu HM, Chou FI. Low dose of gamma irradiation enhanced boronophenylalanine uptake in head and neck carcinoma cells for boron neutron capture therapy. Appl Radiat Isot. 2011;69:1728-31.
15. Oji C, Chukwuneke FN. Oral cancer in Enugu, Nigeria, 1998-2003. Br J Oral Maxillofac Surg. 2007;45:298-301.
16. Ministry of Health and Welfare T. http://wwwmohwgovtw/cht/DOS/Statisticaspx?f_list_no=312&fod_list_no=1717. 2013.
17. Scully C, Bagan JV. Recent advances in Oral Oncology. Oral Oncol. 2007;43:107-15.
18. Ko YC, Huang YL, Lee CH, Chen MJ, Lin LM, Tsai CC. Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med. 1995;24:450-3.
19. Woolgar JA, Scott J, Vaughan ED, Brown JS, West CR, Rogers S. Survival, metastasis and recurrence of oral cancer in relation to pathological features. Annals of the Royal College of Surgeons of England. 1995;77:325-31.
20. Patel SG, Shah JP. TNM staging of cancers of the head and neck: striving for uniformity among diversity. CA Cancer J Clin. 2005;55:242-58; quiz 61-2, 64.
21. Liao CT, Chang JTC, Wang HM, Chen IH, Lin CY, Chen TM, et al. Telomerase as an independent prognostic factor in head and neck squamous cell carcinoma. Head Neck-J Sci Spec. 2004;26:504-12.
22. Liao CT, Chang JTC, Wang HM, Ng SH, Hsueh C, Lee LY, et al. Analysis of risk factors of predictive local tumor control in oral cavity cancer. Ann Surg Oncol. 2008;15:915-22.
23. Liao CT, Kang CJ, Chang JT, Wang HM, Ng SH, Hsueh C, et al. Survival of second and multiple primary tumors in patients with oral cavity squamous cell carcinoma in the betel quid chewing area. Oral Oncol. 2007;43:811-9.
24. Chiou SH, Yu CC, Huang CY, Lin SC, Liu CJ, Tsai TH, et al. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res. 2008;14:4085-95.
25. Barth RF, Soloway AH, Fairchild RG. Boron neutron capture therapy of cancer. Cancer Res. 1990;50:1061-70.
26. Utsumi H, Ichihashi M, Kobayashi T, Elkind MM. Sublethal and potentially lethal damage repair on thermal neutron capture therapy. Pigment Cell Res. 1989;2:337-42.
27. Papaspyrou M, Feinendegen LE, Muller-Gartner HW. Preloading with L-tyrosine increases the uptake of boronophenylalanine in mouse melanoma cells. Cancer Res. 1994;54:6311-4.
28. 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 Res. 1987;47:6377-83.
29. Chou FI, Chung HP, Liu HM, Chi CW, Lui WY. Suitability of boron carriers for BNCT: Accumulation of boron in malignant and normal liver cells after treatment with BPA, BSH and BA. Appl Radiat Isotopes. 2009;67:S105-S8.
30. Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, Nii T, et al. Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta. 2001;1514:291-302.
31. Capala J, Makar MS, Coderre JA. Accumulation of boron in malignant and normal cells incubated in vitro with boronophenylalanine, mercaptoborane or boric acid. Radiat Res. 1996;146:554-60.
32. Obayashi S, Kato I, Ono K, Masunaga S, Suzuki M, Nagata K, et al. Delivery of (10)boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy. Oral Oncol. 2004;40:474-82.
33. Kreimann EL, Itoiz ME, Dagrosa A, Garavaglia R, Farias S, Batistoni D, et al. The hamster cheek pouch as a model of oral cancer for boron neutron capture therapy studies: selective delivery of boron by boronophenylalanine. Cancer Res. 2001;61:8775-81.
34. Kreimann EL, Itoiz ME, Longhino J, Blaumann H, Calzetta O, Schwint AE. Boron neutron capture therapy for the treatment of oral cancer in the hamster cheek pouch model. Cancer Res. 2001;61:8638-42.
35. Molinari AJ, Pozzi EC, Monti Hughes A, Heber EM, Garabalino MA, Thorp SI, et al. "Sequential" boron neutron capture therapy (BNCT): a novel approach to BNCT for the treatment of oral cancer in the hamster cheek pouch model. Radiat Res. 2011;175:463-72.
36. Kamida A, Obayashi S, Kato I, Ono K, Suzuki M, Nagata K, et al. Effects of boron neutron capture therapy on human oral squamous cell carcinoma in a nude mouse model. Int J Radiat Biol. 2006;82:21-9.
37. Bibby MC. Orthotopic models of cancer for preclinical drug evaluation: advantages and disadvantages. Eur J Cancer. 2004;40:852-7.
38. Lin YC, Chen HW, Kuo YC, Chang YF, Lee YJ, Hwang JJ. Therapeutic Efficacy Evaluation of Curcumin on Human Oral Squamous Cell Carcinoma Xenograft Using Multimodalities of Molecular Imaging. Am J Chinese Med. 2010;38:343-58.
39. Christian N, Bol A, De Bast M, Labar D, Lee J, Mahy P, et al. Determination of tumour hypoxia with the PET tracer [18F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model. Eur J Nucl Med Mol Imaging. 2007;34:1348-54.
40. Kiger WS, Lu XQ, Harling OK, Riley KJ, Binns PJ, Kaplan J, et al. Preliminary treatment planning and dosimetry for a clinical trial of neutron capture therapy using a fission converter epithermal neutron beam. Appl Radiat Isotopes. 2004;61:1075-81.
41. Kato I, Ono K, Sakurai Y, Ohmae M, Maruhashi A, Imahori Y, et al. Effectiveness of BNCT for recurrent head and neck malignancies. Appl Radiat Isot. 2004;61:1069-73.
42. Liu YH, Lee PY, Lin YC, Chou FI, Chen WL, Huang YS, et al. Dose estimation of animal experiments at the THOR BNCT beam by NCTPlan and Xplan. Appl Radiat Isot. 2014;In Press.
43. Wang HE, Liao AH, Deng WP, Chang PF, Chen JC, Chen FD, et al. Evaluation of 4-borono-2-F-18-fluoro-L-phenylalanine-fructose as a probe for boron neutron capture therapy in a glioma-bearing rat model. Journal of Nuclear Medicine. 2004;45:302-8.
44. Myers JN, Holsinger FC, Jasser SA, Bekele BN, Fidler IJ. An orthotopic nude mouse model of oral tongue squamous cell carcinoma. Clin Cancer Res. 2002;8:293-8.
45. Qian J, Yang J, Dragovic AF, Abu-Isa E, Lawrence TS, Zhang M. Ionizing radiation-induced adenovirus infection is mediated by dynamin 2. Cancer Research. 2005;65:5493-7.
46. Haase C, Bergmann R, Fuechtner F, Hoepping A, Pietzsch J. L-type amino acid transporters LAT1 and LAT4 in cancer: uptake of 3-O-methyl-6-18F-fluoro-L-dopa in human adenocarcinoma and squamous cell carcinoma in vitro and in vivo. J Nucl Med. 2007;48:2063-71.
47. Heiss P, Mayer S, Herz M, Wester HJ, Schwaiger M, Senekowitsch-Schmidtke R. Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-L-tyrosine in vitro and in vivo. J Nucl Med. 1999;40:1367-73.
48. Brown JM, Giaccia AJ. The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res. 1998;58:1408-16.
49. Brown JM, Siim BG. Hypoxia-Specific Cytotoxins in Cancer Therapy. Seminars in radiation oncology. 1996;6:22-36.
50. Moriyama EH, Niedre MJ, Jarvi MT, Mocanu JD, Moriyama Y, Subarsky P, et al. The influence of hypoxia on bioluminescence in luciferase-transfected gliosarcoma tumor cells in vitro. Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology. 2008;7:675-80.
51. Tan MH, Holyoke ED, Goldrosen MH. Murine Colon Adenocarcinoma - Syngeneic Orthotopic Transplantation and Subsequent Hepatic Metastases. J Natl Cancer I. 1977;59:1537-44.
52. Kerbel RS. Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans - Better than commonly perceived - But they can be improved. Cancer Biol Ther. 2003;2:S134-S9.
53. Killion JJ, Radinsky R, Fidler IJ. Orthotopic models are necessary to predict therapy of transplantable tumors in mice. Cancer Metast Rev. 1998;17:279-84.
54. Fidler IJ. Rationale and Methods for the Use of Nude-Mice to Study the Biology and Therapy of Human Cancer Metastasis. Cancer Metast Rev. 1986;5:29-49.
55. Yuen AP, Lam KY, Wei WI, Ho CM, Chow TL, Yuen WF. A comparison of the prognostic significance of tumor diameter, length, width, thickness, area, volume, and clinicopathological features of oral tongue carcinoma. American journal of surgery. 2000;180:139-43.
56. Yuen AP, Wei WI, Wong YM, Tang KC. Elective neck dissection versus observation in the treatment of early oral tongue carcinoma. Head Neck. 1997;19:583-8.
57. Barth RF, Vicente MGH, Harling OK, Kiger WS, Riley KJ, Binns PJ, et al. Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer. Radiation Oncology. 2012;7:146-67.
58. Imahori Y, Ueda S, Ohmori Y, Sakae K, Kusuki T, Kobayashi T, et al. Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: Part II. Clinical Cancer Research. 1998;4:1833-41.
59. Kashino G, Fukutani S, Suzuki M, Liu Y, Nagata K, Masunaga S, et al. A simple and rapid method for measurement of (10)B-para-boronophenylalanine in the blood for boron neutron capture therapy using fluorescence spectrophotometry. Journal of radiation research. 2009;50:377-82.
60. Hanaoka K, Watabe T, Naka S, Kanai Y, Ikeda H, Horitsugi G, et al. FBPA PET in boron neutron capture therapy for cancer: prediction of B concentration in the tumor and normal tissue in a rat xenograft model. EJNMMI research. 2014;4:70.
61. Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med. 2007;48:932-45.
62. Hoffman EJ, Huang SC, Phelps ME. Quantitation in Positron Emission Computed-Tomography .1. Effect of Object Size. J Comput Assist Tomo. 1979;3:299-308.
63. 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 Res. 1996;56:4302-6.
64. Barth RF, Soloway AH, Fairchild RG, Brugger RM. Boron neutron capture therapy for cancer. Realities and prospects. Cancer. 1992;70:2995-3007.
65. Aihara T, Hiratsuka J, Morita N, Uno M, Sakurai Y, Maruhashi A, et al. First clinical case of boron neutron capture therapy for head and neck malignancies using 18F-BPA PET. Head Neck. 2006;28:850-5.
66. Kabalka GW, Smith GT, Dyke JP, Reid WS, Longford CP, Roberts TG, et al. Evaluation of fluorine-18-BPA-fructose for boron neutron capture treatment planning. J Nucl Med. 1997;38:1762-7.
67. Wang LW, Wang SJ, Chu PY, Ho CY, Jiang SH, Liu YWH, et al. BNCT for locally recurrent head and neck cancer: Preliminary clinical experience from a phase I/II trial at Tsing Hua Open-Pool Reactor. Appl Radiat Isotopes. 2011;69:1803-6.
68. Palmer MR, Goorley JT, Kiger WS, Busse PM, Riley KJ, Harling OK, et al. Treatment planning and dosimetry for the Harvard-MIT Phase I clinical trial of cranial neutron capture therapy. Int J Radiat Oncol. 2002;53:1361-79.
69. Yu HT, Liu YW, Lin TY, Wang LW. BNCT treatment planning of recurrent head-and-neck cancer using THORplan. Appl Radiat Isot. 2011;69:1907-10.
70. Kiger WS, 3rd, Palmer MR, Riley KJ, Zamenhof RG, Busse PM. A pharmacokinetic model for the concentration of 10B in blood after boronophenylalanine-fructose administration in humans. Radiat Res. 2001;155:611-8.
71. Pazirandeh A, Jameie B, Zargar M. Determination of boron distribution in rat's brain, kidney and liver. Appl Radiat Isotopes. 2009;67:S369-S73.
72. Mikado S, Yanagie H, Yasuda N, Higashi S, Ikushima I, Mizumachi R, et al. Application of neutron capture autoradiography to Boron Delivery seeking techniques for selective accumulation of boron compounds to tumor with intra-arterial administration of boron entrapped water-in-oil-in-water emulsion. Nucl Instrum Meth A. 2009;605:171-4.
73. Altieri S, Bortolussi S, Bruschi P, Chiari P, Fossati F, Stella S, et al. Neutron autoradiography imaging of selective boron uptake in human metastatic tumours. Appl Radiat Isotopes. 2008;66:1850-5.
74. Ogura K, Yanagie H, Eriguchi M, Lehmann EH, Kuhne G, Bayon G, et al. Neutron capture autoradiographic study of the biodistribution of 10B in tumor-bearing mice. Appl Radiat Isot. 2004;61:585-90.
75. Arias H, Palacios D, Sajo-Bohus L, Viloria T. Alternative procedure for LR 115 chemical etching and alpha tracks counting. Radiat Meas. 2005;40:357-62.
76. Nikezic D, Yu KN. Profiles and parameters of tracks in the LR 115 detector irradiated with alpha particles. Nuclear Instruments and Methods in Physics Reasearch B. 2002;196:105-12.
77. Dwaikat N, Safarini G, El-hasan M, Iida T. CR-39 detector compared with Kodalpha film type (LR115) in terms of radon concentration. Nucl Instrum Meth A. 2007;574:289-91.
78. Schipper ML, Cheng Z, Lee SW, Bentolila LA, Iyer G, Rao J, et al. microPET-based biodistribution of quantum dots in living mice. J Nucl Med. 2007;48:1511-8.
79. Hsiao M-C, Chen W-L, Tsai P-E, Huang C-K, Liu Y-H, Liu H-M, et al. A preliminary study on using the radiochromic film for 2D beam profile QC/QA at the THOR BNCT facility. Appl Radiat Isotopes. 2011;69:1915-7.
80. Hsiao MC, Jiang SH. A Characterization Study of Gafchromic Ebt Film as a Two-Dimensional Dosimeter. Nucl Technol. 2009;168:191-5.
81. Takahashi Y, Imahori Y, Mineura K. Prognostic and therapeutic indicator of fluoroboronophenylalanine positron emission tomography in patients with gliomas. Clinical Cancer Research. 2003;9:5888-95.
82. Imahori Y, Ueda S, Ohmori Y, Sakae K, Kusuki T, Kobayashi T, et al. Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: Part I. Clinical Cancer Research. 1998;4:1825-32.
83. Linko S, Revitzer H, Zilliacus R, Kortesniemi M, Kouri M, Savolainen S. Boron detection from blood samples by ICP-AES and ICP-MS during boron neutron capture therapy. Scand J Clin Lab Invest. 2008;68:696-702.
84. Laakso J, Kulvik M, Ruokonen I, Vahatalo J, Zilliacus R, Farkkila M, et al. Atomic emission method for total boron in blood during neutron-capture therapy. Clin Chem. 2001;47:1796-803.
85. Santa Cruz GA, Zamenhof RG. The microdosimetry of the B-10 reaction in boron neutron capture therapy: A new generalized theory. Radiation Research. 2004;162:702-10.
86. Ono K, Masunaga SI, Kinashi Y, Takagaki M, Akaboshi M, Kobayashi T, et al. Radiobiological evidence suggesting heterogeneous microdistribution of boron compounds in tumors: its relation to quiescent cell population and tumor cure in neutron capture therapy. Int J Radiat Oncol Biol Phys. 1996;34:1081-6.
87. Yoshida F, Matsumura A, Shibata Y, Yamamoto T, Nakauchi H, Okumura M, et al. Cell cycle dependence of boron uptake from two boron compounds used for clinical neutron capture therapy. Cancer Lett. 2002;187:135-41.
88. Nariai T, Ishiwata K, Kimura Y, Inaji M, Momose T, Yamamoto T, et al. PET pharmacokinetic analysis to estimate boron concentration in tumor and brain as a guide to plan BNCT for malignant cerebral glioma. Appl Radiat Isotopes. 2009;67:S348-S50.
89. Wagner JG. A safe method for rapidly achieving plasma concentration plateaus. Clinical pharmacology and therapeutics. 1974;16:691-700.
90. Eguchi K, Kanazawa K, Shimizudani T, Kanemitsu K, Kaku M. Experimental verification of the efficacy of optimized two-step infusion therapy with meropenem using an in vitro pharmacodynamic model and Monte Carlo simulation. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2010;16:1-9.
91. Hahn RG, Svensen C. Plasma dilution and the rate of infusion of Ringer's solution. British journal of anaesthesia. 1997;79:64-7.
92. Chadha M, Capala J, Coderre JA, Elowitz EH, Iwai J, Joel DD, et al. Boron neutron-capture therapy (BNCT) for glioblastoma multiforme (GBM) using the epithermal neutron beam at the Brookhaven National Laboratory. Int J Radiat Oncol. 1998;40:829-34.
93. Coderre JA, Elowitz EH, Chadha M, Bergland R, Capala J, Joel DD, et al. Boron neutron capture therapy for glioblastoma multiforme using p-boronophenylalanine and epithermal neutrons: Trial design and early clinical results. J Neuro-Oncol. 1997;33:141-52.
94. Kortesniemi M, Seppala T, Auterinen I, Savolainen S. Enhanced blood boron concentration estimation for BPA-F mediated BNCT. Appl Radiat Isot. 2004;61:823-7.
95. Ryynanen PM, Kortesniemi M, Coderre JA, Diaz AZ, Hiismaki P, Savolainen SE. Models for estimation of the (10)B concentration after BPA-fructose complex infusion in patients during epithermal neutron irradiation in BNCT. Int J Radiat Oncol Biol Phys. 2000;48:1145-54.
96. Ono K, Masunaga S, Kinashi Y, Nagata K, Suzuki M, Sakurai Y, et al. Neutron irradiation under continuous BPA injection for solving the problem of heterogeneous distribution of BPA. 12th international congress on neutron capture therapy; 2006; Japan; 2006. p. 27-30.
97. Lauven PM, Kulka PJ. Anaesthesia techniques for midazolam and flumazenil--an overview. Acta anaesthesiologica Scandinavica Supplementum. 1990;92:84-9.

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