選擇性內部放射治療(selective internal radiotherapy, SIRT)是新型癌症治療的潛力股，它將放射源直接置於腫瘤附近，在不會損害健康組織的情況下，直接向惡性細胞提供高劑量輻射，特別是對於化療和外部放射治療的反應很差的癌症，例如深度肝癌。在這類型的應用上，90Y(Yttrium)是首選的元素，因為90Y會發射純β輻射，其在軟組織中的平均範圍為2.5mm，具有可接受的半衰期(64.1h)並且會100%充沛的透過激發中子自然生成89Y。
在本研究中，使用噴霧熱裂解(spray pyrolysis, SP)法合成含有釔的矽酸鹽基粉末。通過X光繞射(X-ray diffraction, XRD)檢測其相組成。使用掃描式電子顯微鏡(scanning electron microscopy, SEM)觀察形貌，接著利用穿透式電子顯微鏡(transmission electron microscopy, TEM)測定其內部結構。使用雙束型聚焦離子束顯微鏡(focused ion beam, FIB)測量釔之分佈狀態。此外，使用傅立葉紅外線光譜(Fourier transform infrared spectroscopy, FTIR)證實了摻雜釔的BG(Y-doped BG, Y-BG)粉末和添加硝酸甘氨酸(glycine nitrate, GN)後的Y-BG粉末的生物活性。此實驗可細分為三個實驗。第一個實驗是使用硝酸釔(yttrium nitrate, YN)和醋酸釔(yttrium acetate, YAc)作為釔來源控制矽酸釔鋁(yttrium aluminium silicate, YAS)玻璃中釔元素的分佈。YN和YAc具有高溶解度，YN衍生的YAS玻璃粉末，釔離子均勻地分散在整個顆粒中；而YAc衍生的YAS玻璃粉末，釔離子則分布在顆粒表面。第二個實驗是在Y-BG粉末中控制釔元素分布。我們發現，對於YN衍生的Y-BG，釔分佈在整個顆粒中，而對於YAc衍生的Y-BG，釔則會集中在顆粒的表面上。另外，YN衍生的Y-BG粉末比YAc衍生的Y-BG粉末和純BG粉末具有更高的生物活性，與觀察到的表面積有直接相關。第三個實驗是使用GN作為造孔劑製備中空的Y-BG粉末。得到的結果表明，添加1M GN的Y-BG粉末由更多的中空顆粒組成，並且具有更高的生物活性。

Selective internal radiotherapy (SIRT) is the potential candidate of novel cancer treatments, which placed the radioactive source directly near the tumor to deliver high doses radiation directly to malignant cells without damaging healthy tissues, especially for cancers where the response to chemotherapy and external radiotherapy is poor like deeply seated liver cancer. For this application 90Y was element of choice, since 90Y emits pure beta radiation, which has an average range of 2.5 mm in soft tissue, has an acceptable half-life (64.1 h) and can be formed by neutron activation of the naturally occurring 89Y, which is 100 % abundant.
In this study, Y contain silicate base powders were synthesized using spray pyrolysis (SP). The phase compositions of these powders were characterized by X-ray diffraction. The morphologies of these glassy powders were observed using scanning electron microscopy (SEM), and then use transmission electron microscopy (TEM) to determine its inner structure. The Y-distribution was measured using focused ion beam (FIB). In addition, the
bioactivities of Y-doped BG and GN- treated Y-doped BG powders were confirmed using Fourier transform infrared spectroscopy (FTIR). The experiment can be subdivided into three experiments. The first experiment was control of Y-distribution in the yttrium aluminium silicate (YAS) glass using yttrium nitrate(YN) and yttrium acetate (YAc) salts as Y sources. Because of YN and YAc salts have high solubility, Y ion dispersed homogenously throughout the particle for YN -derived YAS glassy powder case, where as it distributed at surface of particle for YAc-derived YAS glassy powder. The second experiment was controlling of Y in Y-doped bioactive glass (Y-BG) powders. We found that for YN- derived Y-doped BG, Y distributed simultaneously in the whole particle whereas for YAc- derived Y-doped BG, Y-concentrated on the surface of particle. In addition, YN
derived Y-doped BG powder has high bioactivity than YAc -derived Y-doped BG powder and pure BG powder, correlating directly with the observed surface areas. The third experiment was preparation of hollow Y-doped BG powder using glycine nitrate (GN) as hollow forming agent. The obtained result indicates that 1M GN-treated Y-doped BG powder consists more fraction of hollow particles and also better in bioactivity.

[1] N. Borrelli, A. Luderer, J. Panzarino, H. Rittler, Magnetic Glass-Ceramics for Tumor-Therapy by Hyperthermia, American Ceramic Society Bulletin, 735 (1982), 819-819.
[2] C.S. Kumar, F. Mohammad, Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery, Advanced drug delivery reviews, 63 (2011) 789-808.
[3] C.-H. Yeong, M.-h. Cheng, K.-H. Ng, Therapeutic radionuclides in nuclear medicine: current and future prospects, Journal of Zhejiang University Science B, 15 (2014) 845-863.
[4] G.J. Ehrhardt, D.E. Day, Therapeutic use of 90Y microspheres, International Journal of Radiation Applications and Instrumentation. Part B. Nuclear Medicine and Biology, 14 (1987) 233-242.
[5] V.R. Sinha, V. Goyel, A. Trehan, Radioactive microspheres in therapeutics, Die Pharmazie An International Journal of Pharmaceutical Sciences, 59 (2004) 419-426.
[6] P. Jander, W.S. Brocklesby, Spectroscopy of yttria-alumina-silica glass doped with thulium and erbium, IEEE Journal of Quantum Electronics, 40 (2004) 509-512.
[7] V. Simon, D. Eniu, A. Takács, K. Magyari, M. Neumann, S. Simon, Iron doping effect on the electronic structure in yttrium aluminosilicate glasses, Journal of Non-Crystal Solids, 351 (2005) 2365-2372.
[8] F.F. Sene, J.R. Martinelli, E. Okuno, Synthesis and characterization of phosphate glass microspheres for radiotherapy applications, Journal of Non-Crystalline Solids, 354 (2008) 4887-4893.
[9] M.B. Bortot, S. Prastalo, M. Prado, Production and Characterization of Glass Microspheres for Hepatic Cancer Treatment, Procedia Materials Science, 1 (2012) 351-358.
[10] M. Ghahramani, A. Garibov, T. Agayev, Production of yttrium aluminum silicate microspheres by gelation of an aqueous solution containing yttrium and aluminum ions in silicone oil, International Journal of Radiation Research, 12 (2014) 189.
[11] J.K. Christie, A. Tilocca, Short-Range Structure of Yttrium Alumino-Silicate Glass for Cancer Radiotherapy: Car-Parrinello Molecular Dynamics Simulations, Advanced Engineering Materials, 12 (2010) B326-B330.
[12] J.K. Christie, A. Tilocca, Aluminosilicate Glasses As Yttrium Vectors for in situ Radiotherapy: Understanding Composition-Durability Effects through Molecular Dynamics Simulations, Chemistry of Materials, 22 (2010) 3725-3734.
[13] E.M. Erbe, D.E. Day, Chemical durability of Y2O3‐Al2O3‐SiO2 glasses for the in vivo delivery of beta radiation, Journal of biomedical materials research, 27 (1993) 1301-1308.
[14] M.L. Smits, J.F. Nijsen, M.A. van den Bosch, M.G. Lam, M.A. Vente, J.E. Huijbregts, A.D. van het Schip, M. Elschot, W. Bult, H.W. de Jong, P.C. Meulenhoff, B.A. Zonnenberg, Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial, Journal of Experimental and Clinical Cancer Research, 29 (2010) 70.
[15] A. Tilocca, Realistic models of bioactive glass radioisotope vectors in practical conditions: Structural effects of ion exchange, The Journal of Physical Chemistry C, 119 (2015) 27442-27448.
[16] L.L. Hench, J.M. Polak, Third-Generation Biomedical Materials, Science, 295 (2002) 1014.
[17] B. Lei, X. Chen, Y. Wang, N. Zhao, G. Miao, Z. Li, C. Lin, Fabrication of porous bioactive glass particles by one step sintering, Materials Letters, 64 (2010) 2293-2295.
[18] M. Ghahramani, A. Garibov, T. Agayev, Production and quality control of radioactive yttrium microspheres for medical applications, Applied Radiation and Isotopes, 85 (2014) 87-91.
[19] J.K. Christie, J. Malik, A. Tilocca, Bioactive glasses as potential radioisotope vectors for in situ cancer therapy: investigating the structural effects of yttrium, Physical Chemistry Chemical Physics, 13 (2011) 17749-17755.
[20] S.-J. Shih, Y.-Y. Wu, C.-Y. Chen, C.-Y. Yu, Morphology and formation mechanism of ceria nanoparticles by spray pyrolysis, Journal of Nanoparticle Research, 14 (2012) 879.
[21] S.-J. Shih, Y.-J. Yu, Y.-Y. Wu, Manipulation of Dopant Distribution in Yttrium-Doped Ceria Particles, Journal of Nanoscience and Nanotechnology, 12 (2012) 7954-7962.
[22] R. Baskar, K.A. Lee, R. Yeo, K.W. Yeoh, Cancer and radiation therapy: current advances and future directions, International Journal of Med Sci, 9 (2012) 193-199.
[23] J. Ferlay, H.R. Shin, F. Bray, D. Forman, C. Mathers, D.M. Parkin, Globocan 2008, cancer incidence and mortality worldwide: IARC Cancer Base No. 10, Lyon, France: International Agency for Research on Cancer, 2 (2010) 895-901
[24] A. Jemal, F. Bray, M.M. Center, J. Ferlay, E. Ward, D. Forman, Global cancer statistics, CA: a cancer journal for clinicians, 61 (2011) 69-90.
[25] O.S. Nielsen, M. Horsman, J. Overgaard, A future for hyperthermia in cancer treatment, European Journal of Cancer, 37 (2001) 1587-1589.
[26] R.D. Aspasio, R. Borges, J. Marchi, Biocompatible glasses for cancer treatment, Biocompatible Glasses, Springer 53 (2016) 249-265.
[27] S.C. Moore, I.-M. Lee, E. Weiderpass, P.T. Campbell, J.N. Sampson, C.M. Kitahara, S.K. Keadle, H. Arem, A.B. de Gonzalez, P. Hartge, Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults, JAMA internal medicine, 176 (2016) 816-825.
[28] C. A. Hoefnagel, Radionuclide therapy revisited,European journal of nuclear medcine, 18 (1991) 408-431.
[29] D. E. Troutner, Chemical and physical properties of radionuclides, journal of radation applications and instrumentation,14 (1987) 171-176.
[30] W. Volkert, W. Goeckeler, G. Ehrhardt, A. Ketring, Therapeutic radionuclides: production and decay property considerations, Journal of nuclear medicine: official publication, Society of Nuclear Medicine, 32 (1991) 174-185.
[31] A. Kassis, J. Adelstein, Radiobiologic principles in radionuclide therapy, journal of nuclear medcine, 46 (2005) 4S-12S.
[32] J. Zweit, Radionuclides and carrier molecules for therapy, Physics in medicne and biology,41 (1996) 10.
[33] S.M. Qaim, Therapeutic radionuclides and nuclear data, Radiochimica Acta, 89 (2001) 297-304.
[34] D.E. Day, T.E. Day, Radiotherapy glasses, Advanced Series in Ceramics, 1 (1993) 305-318.
[35] J.E. White, D.E. Day, Rare earth aluminosilicate glasses for in vivo radiation delivery, Key Engineering Materials, Trans Tech Publ, 94-95 (1994), 181-208.
[36] E.M. Erbe, D.E. Day, Properties of Sm2O3─ Al2O3─ SiO2 glasses for in vivo applications, Journal of the American Ceramic Society, 73 (1990) 2708-2713.
[37] E.M. Erbe, Structure and Properties of Y2O3-Al2O3-SiO2 Glasses, University of Missouri Rolla, Doctoral Dissertations 1991, 993.
[38] J.K. Christie, A. Tilocca, Integrating biological activity into radioisotope vectors: molecular dynamics models of yttrium-doped bioactive glasses, Journal of Materials Chemistry, 22 (2012) 12023-12031.
[39] L.L. Hench, R.J. Splinter, W. Allen, T. Greenlee, Bonding mechanisms at the interface of ceramic prosthetic materials, Journal of biomedical materials research, 5 (1971) 117-141.0
[40] M.N. Rahaman, D.E. Day, B.S. Bal, Q. Fu, S.B. Jung, L.F. Bonewald, A.P. Tomsia, Bioactive glass in tissue engineering, Acta biomaterialia, 7 (2011) 2355-2373.
[41] L.H. Larry, Bioceramics: from concept to clinic, Journal America Ceramic Socity, 74 (1991) 1487-1510.
[42] W.S. Roberto, M.M. Pereira, T.P. Campos, Structure and dosimetric analysis of biodegradable glasses for prostate cancer treatment, Artificial organs, 27 (2003) 432-436.
[43] M. Cerruti, D. Greenspan, K. Powers, Effect of pH and ionic strength on the reactivity of Bioglass® 45S5, Biomaterials, 26 (2005) 1665-1674.
[44] B.A. Ben-Arfa, I.M.M. Salvado, J.M. Ferreira, R.C. Pullar, The effect of functional ions (Y3+, F−, Ti4+) on the structure, sintering and crystallization of diopside-calcium pyrophosphate bioglasses, Journal of Non-Crystalline Solids, 443 (2016) 162-171.
[45] J. Nijsen, A.v.h. Schip, W. Hennink, D. Rook, P. Van Rijk, J. Klerk, Advances in nuclear oncology: microspheres for internal radionuclide therapy of liver tumours, Current medicinal chemistry, 9 (2002) 73-82.
[46] D. Cacaina, H. Ylänen, M. Hupa, S. Simon, Study of yttrium containing bioactive glasses behaviour in simulated body fluid, Journal of Materials Science: Materials in Medicine, 17 (2006) 709-716.
[47] D. Cacaina, H. Ylänen, S. Simon, M. Hupa, The behaviour of selected yttrium containing bioactive glass microspheres in simulated body environments, Journal of Materials Science: Materials in Medicine, 19 (2008) 1225-1233.
[48] C. Ergun, T.J. Webster, R. Bizios, R.H. Doremus, Hydroxylapatite with substituted magnesium, zinc, cadmium, and yttrium. I. Structure and microstructure, Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, 59 (2002) 305-311.
[49] T.J. Webster, C. Ergun, R.H. Doremus, R. Bizios, Hydroxylapatite with substituted magnesium, zinc, cadmium, and yttrium. II. Mechanisms of osteoblast adhesion, Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, 59 (2002) 312-317.
[50] A. Tilocca, N.H. de Leeuw, Ab initio molecular dynamics study of 45S5 bioactive silicate glass, The Journal of Physical Chemistry B, 110 (2006) 25810-25816.
[51] A. Costantini, R. Fresa, A. Buri, F. Branda, Effect of the substitution of Y2O3 for CaO on the bioactivity of 2.5 CaO· 2SiO2 glass, Biomaterials, 18 (1997) 453-458.
[52] D. Lide, H. Frederikse, Handbook of Chemistry and Physics 78th Edition 1997-1998, CRC Press, Boca Raton.
[53] A. Tilocca, A.N. Cormack, N.H. de Leeuw, The structure of bioactive silicate glasses: new insight from molecular dynamics simulations, Chemistry of materials, 19 (2007) 95-103.
[54] A. Tilocca, Models of structure, dynamics and reactivity of bioglasses: a review, Journal of Materials Chemistry, 20 (2010) 6848-6858.
[55] P. Jund, W. Kob, R. Jullien, Channel diffusion of sodium in a silicate glass, Physical Review B, 64 (2001) 134303.
[56] A. Tilocca, Sodium migration pathways in multicomponent silicate glasses: Car–Parrinello molecular dynamics simulations, The Journal of chemical physics, 133 (2010) 014701.
[57] C. Huang, A. Cormack, Structural differences and phase separation in alkali silicate glasses, The Journal of chemical physics, 95 (1991) 3634-3642.
[58] G. Greaves, EXAFS and the structure of glass, Journal of Non-Crystalline Solids, 71 (1985) 203-217.
[59] D.S. Jung, Y.N. Ko, Y.C. Kang, S.B. Park, Recent progress in electrode materials produced by spray pyrolysis for next-generation lithium ion batteries, Advanced Powder Technology, 25 (2014) 18-31.
[60] G.L. Messing, S.-C. Zhang, G.V. Jayanthi, Ceramic Powder Synthesis by Spray Pyrolysis, Journal of the American Ceramic Society, 76 (1993) 2707-2726.
[61] J. Bogovic, S. Stopic, B. Friedrich, J. Schroeder, Ultrasonic spray pyrolysis, Proceedings of EMC, 3 (2011) 1-12.
[62] D. Charlesworth, W. Marshall Jr, Evaporation from drops containing dissolved solids, AIChE Journal, 6 (1960) 9-23.
[63] T.J. Gardner, D. Sproson, G. Messing, Precursor chemistry effects on development of particulate morphology during evaporative decomposition of solutions, MRS Online Proceedings Library Archive, 32 (1984) 227
[64] B. Cullity, S. Stock, Elements of X-ray diffraction. 3rd ed 2001, ISBN No: 0-201-61091-4.
[65] W.H. Bragg, W.L. Bragg, The reflection of X-rays by crystals, Procedings of the royal Socity Lond. A, 88 (1913) 428-438.
[66] S. Brunauer, P.H. Emmett, E. Teller, Adsorption of gases in multimolecular layers, Journal of the American chemical society, 60 (1938) 309-319.
[67] I. Langmuir, The adsorption of gases on plane surfaces of glass, mica and platinum, Journal of the American Chemical society, 40 (1918) 1361-1403.
[68] J. Goldstein, Practical scanning electron microscopy: electron and ion microprobe analysis, Springer Science & Business Media 2012.
[69] Y. Leng, Materials characterization: Introduction to microscopic and spectroscopic methods, John Wiley & Sons 2009.
[70] D.B. Williams, C.B. Carter, The transmission electron microscope, Transmission electron microscopy, Springer 1996, 3-17.
[71] B.-J. Hong, S.-J. Shih, Novel pore-forming agent to prepare of mesoporous bioactive glass using one-step spray pyrolysis, Ceramics International, 43 (2017) S771-S775.
[72] B. Lei, X. Chen, Y. Wang, N. Zhao, C. Du, L. Fang, Synthesis and bioactive properties of macroporous nanoscale SiO2–CaO–P2O5 bioactive glass, Journal of Non-Crystalline Solids, 355 (2009) 2678-2681.
[73] K. Zheng, A. Solodovnyk, W. Li, O.M. Goudouri, C. Stähli, S.N. Nazhat, A.R. Boccaccini, Aging time and temperature effects on the structure and bioactivity of gel‐derived 45S5 glass‐ceramics, Journal of the American Ceramic Society, 98 (2015) 30-38.
[74] C. Shih, H. Chen, L. Huang, P. Lu, H. Chang, I. Chang, Synthesis and in vitro bioactivity of mesoporous bioactive glass scaffolds, Materials Science and Engineering: C, 30 (2010) 657-663.
[75] R. Purohit, B. Sharma, K. Pillai, A. Tyagi, Ultrafine ceria powders via glycine-nitrate combustion, Materials Research Bulletin, 36 (2001) 2711-2721.
[76] S.-J. Shih, W.-L. Tzeng, W.-L. Kuo, Fabrication of ceria particles using glycine nitrate spray pyrolysis, Surface and Coatings Technology, 259 (2014) 302-309.
[77] S.-J. Shih, Y.-C. Lin, S.-H. Lin, P. Veteška, D. Galusek, W.-H. Tuan, Preparation and characterization of Eu-doped gehlenite glassy particles using spray pyrolysis, Ceramics International, 42 (2016) 11324-11329.
[78] S.-J. Shih, Y.-C. Lin, S.-H. Lin, C.-Y. Yu, Correlation of morphology and photoluminescence properties of gehlenite: Eu glassy phosphors, International Journal of Applied Ceramic Technology, 14 (2017) 56-62.
[79] G.L. Messing, S.C. Zhang, G.V. Jayanthi, Ceramic powder synthesis by spray pyrolysis, Journal of the American Ceramic Society, 76 (1993) 2707-2726.
[80] J. Helgorsky, Solubilities Data Series—Volume 13: Scandium, Yttrium, Lanthanum and Lanthanide Nitrates: S. Siekierski, M. Salomon and T. Mioduski (Editors), Pergamon, London, 1983, ISBN 0 08 026192 2, Elsevier, 1985.
[81] S.-J. Shih, W.-L. Tzeng, Manipulation of morphology of strontium titanate particles by spray pyrolysis, Powder technology, 264 (2014) 291-297.
[82] J. Farjas, J. Camps, P. Roura, S. Ricart, T. Puig, X. Obradors, Thermoanalytical study of the formation mechanism of yttria from yttrium acetate, Thermochimica Acta, 521 (2011) 84-89.
[83] S.-J. Shih, P.R. Herrero, G. Li, C.-Y. Chen, S. Lozano-Perez, Characterization of mesoporosity in ceria particles using electron microscopy, Microscopy and Microanalysis, 17 (2011) 54-60.
[84] S.-J. Shih, Y.-J. Chou, C.-Y. Chen, C.-K. Lin, One-step synthesis and characterization of nanosized bioactive glass, Journal of Medical Bio. Enginering 34 (2014) 18-23.
[85] S.-J. Shih, L.-Y.S. Chang, C.-Y. Chen, K.B. Borisenko, D.J.H. Cockayne, Nanoscale yttrium distribution in yttrium-doped ceria powder, Journal of Nanoparticles Research, 11 (2009) 2145-2152.
[86] S.-J. Shih, G. Li, D.J.H. Cockayne, K.B. Borisenko, Mechanism of dopant distribution: An example of nickel-doped ceria nanoparticles, Scripta Materialia., 61 (2009) 832-835.
[87] Yttrium acetate (MSDS No. 23363-14-6) chemical books, bejing,china (2017).
[88] P. Melnikov, V.A. Nascimento, L.Z.Z. Consolo, A.F. Silva, Mechanism of thermal decomposition of yttrium nitrate hexahydrate, Y(NO3)3·6H2O and modeling of intermediate oxynitrates, Journal of Thermal Analysis and Calorimetry, 111 (2013) 115-119.
[89] B. T.Kilbourn, A Lanthanide Lantology, Molycorp, Inc., Mountain Pass (1993).
[90] J. Helgorsky, Solubilities data series of scandium, yttrium, lanthanum and lanthanide nitrates, Journal of International union of pure and applied chemistry, 13 (1983) 20-26.
[91] B. Kilbourn, Part 1, A–L, A lanthanide lantology. Molycorp Inc., Mountain Pass, 4 (1993).
[92] A. Hadush Tesfay, Y.-J. Chou, C.-Y. Tan, F. Fufa Bakare, N.-T. Tsou, E.-W. Huang, S.-J. Shih, Control of Dopant Distribution in Yttrium-Doped Bioactive Glass for Selective Internal Radiotherapy Applications Using Spray Pyrolysis, Materials, 12 (2019) 986.
[93] Citric acid.CAS 77-92-9;Pubchem.Avilab online:https://pubchem.ncbi.nlm.nih.gov/compound/citric_acid#section=Physical-Description.
[94] H. Talukdar, S. Rudra, K.K. Kundu, Thermodynamics of transfer of glycine, diglycine, and triglycine from water to aqueous solutions of urea, glycerol, and sodium nitrate, Canadian journal of chemistry, 66 (1988) 461-468.