放射性核種的產製是一重要議題，可被廣泛運用在諸多不可或缺的醫療用途，主要為醫學造影與核醫藥物。本研究從核反應物理的角度深入探討放射性核種的產製，以中低能量質子迴旋加速器可生產之核種為主，相關的成果與經驗有利於產製流程的預測與最佳化。文獻中常用於核種產製的反應分析程式有二大類：單純的核反應截面計算程式(例
如ALICE、EMPIRE 與Talys 等) 與多用途的蒙地卡羅粒子遷移程式(例如FLUKA、PHITS 與MCNP 等)，本研究選擇使用Talys 與自行開發之輔助程式TalysSup 進行一系列有興趣之核種產製流程的產率預測及相關參數的敏感度研究分析。

Talys 程式內建有數個不同的核反應模型，為了驗證計算的可靠性與不同核反應模型選擇的適用性，本研究首先彙整IAEA-TECDOC-1211 報告中所有的實驗數據並利用Talys 逐一分析，嘗試歸納針對不同質子能量區間與不同靶材原子序範圍的Talys 最適計算模型，以供後續使用者參考。台灣即將建置新的70 MeV 迴旋加速器，目前有興趣產製的放射性核種包括Tl-201、I-123、Sr-82、Ac-225、Cu-67 和Sn-117m，本研究利用驗證最適的Talys 計算模型逐一分析上述六個核種的可能產製途徑，並透過一系列敏感度研究分析回報最佳產製的照射條件與冷卻分離時間，期望在合理的雜質不純度下達到
最高的目標產物產率。為了能夠更有效率使用Talys 進行上述分析，本研究亦開發出相應的自動計算輔助軟體TalysSup 以及圖形化介面TalysGUI，協助開發者將Talys 計算之作用截面與產率評估所需之阻擋本領結合，達成自動化分析的效果，有利於使用者快速探討各放射性核種產製的物理條件與流程。

The production of radioisotopes is an important issue that can be widely used in many essential medical applications, mainly in medical imaging and nuclear medicine. This study delves into the production of radioisotopes from the perspective of nuclear reaction physics, focusing primarily on isotopes that can be produced using medium to low-energy proton cyclotrons. The findings and experiences related to the production process are beneficial for predicting and optimizing the production flow. There are two major types of reaction analysis programs commonly used in the literature for isotope production: standalone nuclear reaction cross-section calculation programs (such as ALICE, EMPIRE, and Talys) and multipurpose Monte Carlo particle transport programs (such as FLUKA, PHITS, and MCNP). In this study, Talys and a self-developed auxiliary program called TalysSup were chosen to perform a series of rate predictions for the interested isotope production processes and sensitivity studies of related parameters.

Talys program includes several different nuclear reaction models. To verify the reliability of the calculations and the suitability of different nuclear reaction models, this study first compiled all the experimental data from IAEA-TECDOC-1211 report and analyzed them one by one using Talys. The aim was to deduce the most appropriate Talys calculation models for different proton energy ranges and atomic number ranges of target materials, for reference by subsequent users.
Taiwan is about to establish a new 70 MeV cyclotron, and the radioisotopes of interest for production include Tl-201, I-123, Sr-82, Ac-225, Cu-67, and Sn-117m. This study utilized the validated optimal Talys calculation models to analyze the potential production pathways for these six isotopes and reported the best irradiation conditions and cooling separation times through a series of sensitivity studies. The goal is to achieve the highest target product yield with easonable impurity levels. In order to efficiently use Talys for the aforementioned analyses, this study also developed a corresponding automated calculation support software, TalysSup, and the graphic user interface, TalysGUI, to assist developers in combining the cross-sections calculated by Talys with the stopping power required for ield assessment, achieving automated analysis and facilitating rapid exploration of the physical conditions and processes for the production of various radioisotopes.

摘要 i
Abstract ii
誌謝 iv
目錄 v
表目錄 vii
圖目錄 viii
第一章 緒論 1
1.1 加速器應用 1
1.2 核反應參數 3
1.2.1 微觀作用截面 3
1.2.2 阻擋本領 4
1.2.3 產率 4
1.3 文獻回顧與研究動機 5
第二章 方法與工具介紹 8
2.1 作用截面 8
2.1.1 入射能量低於 0.2MeV 9
2.1.2 入射能量在 0.2 到 4MeV 之間 9
2.1.3 入射能量在 4 到 8MeV 之間 10
2.1.4 入射能量大於 8MeV 11
2.1.5 入射能量超過 40MeV 11
2.2 核能階密度 11
2.2.1 FGM 12
2.2.2 CTM 13
2.2.3 BFM 13
2.2.4 GSM 14
2.2.5 HFB 15
2.3 阻擋本領 16
2.3.1 貝特公式 16
2.3.2 NIST 17
2.3.3 蒙特卡羅法 17
2.4 Talys 19
2.4.1 基本參數 19
2.4.2 進階參數 20
2.5 產製方法與流程 21
第三章 Talys 的使用與驗證 22
3.1 IAEA-TECDOC-1211 核種產製反應截面 23
3.1.1 光子放射源 23
3.1.2 正子放射源 40
3.2 Talys 輸出活度隨時間變化 47
3.3 驗證差異與趨勢觀察 48
第四章 Talys 輔助程式的開發與應用 50
4.1 Talys 輔助程式 51
4.1.1 圖形化介面 (TalysGUI) 51
4.1.2 自動化分析 (TalysSup) 53
4.2 201Tl 產製 57
4.3 123I 產製 61
4.3.1 127I(p,5n)123Xe−→123I 61
4.3.2 124Xe(p,pn/2n)123Xe/123Cs−→123I 64
4.4 82Sr 產製 70
4.5 225Ac 產製 74
4.5.1 226Ra(p,2n)225Ac 74
4.5.2 232Th(p,α4n)225Ac 77
4.6 67Cu 產製 81
4.6.1 natZn(p,xpxn) 81
4.6.2 三明治產製法 84
4.7 117mSn 產製 88
第五章 結論與未來工作 92
5.1 結論 92
5.2 未來工作 92
參考資料 94
附錄 A 程式碼 99
A.1 Talys 99
A.1.1 203Tl(p,3n)201Pb−→201Tl 99
A.1.2 127I(p,5n)123Xe−→123I 99
A.1.3 124Xe(p,pn/2n)123Xe/123Cs−→123I 100
A.1.4 natRb(p,xn)82Sr 101
A.1.5 226Ra(p,2p)225Ac 101
A.1.6 232Th(p,α4n)225Ac 102
A.1.7 natZn(p,xpα) 67Cu 103
A.1.8 natSb(p,xnα) 117mSn 103
A.2 TalysGUI 104

[1] International Atomic Energy Agency, Charged Particle Cross-Section Database for Medical Radioisotope Production: Diagnostic Radioisotopes and Monitor Reactions. No. 1211 in TECDOC Series, Vienna: IAEA, 05 2001.
[2] M. Sahagia, A. Luca, A. Antohe, M.-R. Ioan, C. Cîmpeanu, C. Barna, and C. Ivan, “Standardisation of a 68(Ge+Ga) solution within the CCRI(II)-K2.Ge-68 key comparison,” Journal of Radioanalytical and Nuclear Chemistry, vol. 311, pp. 983–990, 02 2017.
[3] 高梓木, 「國家中子與質子科學應用研究：核研所 70 MeV 中型迴旋加速器建置計畫簡介」. 核能研究所所務發展諮議委員會, 2021.
[4] 行政院原子能委員會, 「行政院原子能委員會 110 年第 4 次委員會議紀錄」. 行政院原子能委員會會議紀錄, 2021.
[5] E. Buthelezi, F. Nortier, and I. Schroeder, “Excitation functions for the production of 82Sr by proton bombardment of natRb at energies up to 100MeV,” Applied Radiation and Isotopes, vol. 64, no. 8, pp. 915–924, 2006.
[6] C. Apostolidis, R. Molinet, J. McGinley, K. Abbas, J. Möllenbeck, and A. Morgenstern, “Cyclotron production of Ac-225 for targeted alpha therapy,” Applied Radiation and Isotopes, vol. 62, no. 3, pp. 383–387, 2005.
[7] L. Mausner, K. Kolsky, V. Joshi, and S. Srivastava, “Radionuclide development at bnl for nuclear medicine therapy,” Applied Radiation and Isotopes, vol. 49, no. 4, pp. 285–294, 1998.
[8] L. Mou, P. Martini, G. Pupillo, I. Cieszykowska, C. S. Cutler, and R. Mikołajczak, “67Cu production capabilities: A mini review,” Molecules, vol. 27, no. 5, p. 1501, 2022.
[9] R. Sheu, S. Jiang, and T. Duh, “Evaluation of thallium-201 production in INER＇s compact cyclotron based on excitation functions,” Radiation Physics and Chemistry, vol. 68, no. 5,
pp. 681–688, 2003.
[10] J. E. Turner, Interaction of Heavy Charged Particles with Matter, ch. 5, pp. 109–137. John Wiley & Sons, Ltd, 2007.
[11] E. Tel, Y. Kavun, H. Özdoğan, and A. Kaplan, “Energy spectrum of 208Pb(n,x) reactions,” AIP Conference Proceedings, vol. 1935, p. 180001, 02 2018.
[12] A. Konobeyev and U. Fischer, “Global comparison of TALYS and ALICE code calculations with measured neutron and proton induced reaction cross- sections at energies up to 150 mev,” Neutron Measurements, Evaluations and Applications. Nuclear Data for Sustainable Nuclear Energy (NEMEA-5), pp. 57–60, 10 2008.
[13] H. Sun, R. Han, B. Liu, Z. Chen, B. Yang, X. Zhang, G. Tian, F. Shi, and P. Luo, “Thick target yields of proton induced reactions on natural molybdenum,” Applied Radiation and Isotopes, vol. 190, p. 110474, 2022.
[14] A. Koning, S. Hilaire, and S. Goriely, “TALYS-1.96/2.0: Simulation of nuclear reactions,” 2021.
[15] J. Townsend, A Modern Approach to Quantum Mechanics. University Science Books, 2012.
[16] J. D. Jackson, Classical electrodynamics. New York, NY: Wiley, 3rd ed. ed., 2021.
[17] M. A.J.Koning, “A global pre-equilibrium analysis from 7 to 200 mev based on the optical
model potential,” Nuclear Physics A, vol. 744, pp. 15–76, 2004.
[18] D. J. Griffiths, Introduction to elementary particles; 2nd rev. version. Physics textbook, New York, NY: Wiley, 2008.
[19] A. Behkami and Z. Kargar, “Nuclear level density at high spin and excitation energy,” Communications in Theoretical Physics, vol. 36, p. 305, 09 2001.
[20] W. Dilg, W. Schantl, H. Vonach, and M. Uhl, “Level density parameters for the backshifted fermi gas model in the mass range 40 < a < 250,” Nuclear Physics A, vol. 217, no. 2, pp. 269–298, 1973.
[21] S. Goriely, S. Hilaire, M. Girod, and S. Péru, “First Gogny-Hartree-Fock-Bogoliubov nuclear mass model,” Physical Review Letters, vol. 102, p. 242501, 06 2009.
[22] P. Reinhard, M. Bender, K. Rutz, and J. Maruhn, “An HFB scheme in natural orbitals,” Zeitschrift für Physik A Hadrons and Nuclei, vol. 358, pp. 277–278, 08 1997.
[23] S. Goriely, N. Chamel, and J. M. Pearson, “Skyrme-Hartree-Fock-Bogoliubov nuclear mass formulas: Crossing the 0.6 mev accuracy threshold with microscopically deduced pairing,” Physical Review Letters, vol. 102, p. 152503, 4 2009.
[24] M. Anguiano, A. M. Lallena, G. Co’, V. de Donno, M. Grasso, and R. N. Bernard, “Gogny interactions with tensor terms,” European Physical Journal A, vol. 52, no. 7, p. 183, 2016.
[25] M. B. . J. C. . M. Z. . J. Chang”, “Stopping-Power & Range Tables for Electrons, Protons, and Helium Ions,” Physical Measurement Laboratory, 07 2017.
[26] R. Stoller, M. Toloczko, G. Was, A. Certain, S. Dwaraknath, and F. Garner, “On the use of SRIM for computing radiation damage exposure,” Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, vol. 310,
pp. 75–80, 2013.
[27] I. Gaye, S. Yanhdet, D. Gaye, A. Diallo, A. S. Bouzou, and M. Wade, “SRIM simulation of the interaction of heavy ions 36Ar, 78Kr, 136Xe and 238U with silicon material,” International Journal of Innovation and Applied Studies, vol. 37, no. 3, pp. 450–460, 2022.
[28] D. Rochman, A. J. Koning, S. C. van der Marck, A. Hogenbirk, and D. van Veen, “Nuclear data uncertainty propagation: Total monte carlo vs. covariances,” Journal of the Korean Physical Society, vol. 59, pp. 1236–1241, 08 2011. (Received 26 April 2010).
[29] A. Dash, M. R. A. Pillai, and F. F. R. Knapp, “Production of 177lu for targeted radionuclide therapy: Available options,” Nuclear Medicine and Molecular Imaging, vol. 49, pp. 85–107, 2015.
[30] G. Crișan, N. S. Moldovean-Cioroianu, D.-G. Timaru, G. Andrieș, C. Căinap, and V. Chiș, “Radiopharmaceuticals for pet and spect imaging: A literature review over the last decade,” International Journal of Molecular Sciences, vol. 23, no. 9, 2022.
[31] 鄭澄意,「正子斷層造影簡介」. 三軍總醫院, 03 2023. https://wwwv.tsgh.ndmctsgh.edu.tw/unit/10015/24211.
[32] D. Syme, E. Wood, I. Blair, S. Kew, M. Perry, and P. Cooper, “Yield curves for cyclotron production of 123I, 125I and 121I by 127I (p,xn) Xe → (β) → I reactions,” The International Journal of Applied Radiation and Isotopes, vol. 29, p. 29–38, 01 1978.
[33] K. Suzuki, “Production of pure 123I by the 127I(p,5n)123Xe→ 123I reaction,” Radioisotopes, vol. 35, no. 5, pp. 235–241, 1986.
[34] S. Wilkins, S. Shimore, H. Hines, J. Jungerman, F. Hegedus, and G. DeNardo, “Excitation functions and yields for 123I production using the 127I(p, 5n) 123Xe reaction,” The International Journal of Applied Radiation and Isotopes, vol. 26, no. 5, pp. 279–283, 1975.
[35] A. Nikjou and M. Sadeghi, “Overview and evaluation of different nuclear level density models for the 123I radionuclide production,” Applied Radiation and Isotopes, vol. 136, pp. 45–58, 2018.
[36] J. Husson, Y. Legoux, and C. Liang, “Study of the rate of formation of short-lived iodine and xenon isotopes at the synchrocyclotron of orsay for use in medicine,” Inst Phys Nucl
Orsay, vol. 27, no. 78, pp. 1–11, 1978.
[37] T. Kakavand, M. Sadeghi, K. Moghaddam, S. Bonab, and B. Fateh, “Computer simulation techniques to design Xenon-124 solid target for Iodine-123 production,” J. Radiat. Res, vol. 5, pp. 207–2, 03 2008.
[38] N. V. Kurenkov, A. B. Malinin, A. Sebyakin, and N. I. Venikov, “Excitation functions of proton-induced nuclear reactions on 124Xe: Production of 123I,” Journal of Radioanalytical and Nuclear Chemistry, vol. 135, pp. 39–50, 1989.
[39] F. Tárkányi, S. Qaim, G. Stöcklin, M. Sajjad, R. Lambrecht, and H. Schweickert, “Excitation functions of (p, 2n) and (p, pn) reactions and differential and integral yields of 123I in proton induced nuclear reactions on highly enriched 124Xe,” International Journal
of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes, vol. 42, no. 3, pp. 221–228, 1991.
[40] A. Witsenboer, J. Goeij, and S. Reiffers, “Production of Iodine-123 via proton irradiation of 99.8% enriched Xenon-124,” Labelled Compounds and Radiopharmaceuticals, vol. 23, pp. 1284–1285, 01 1986.
[41] D. J. Jamriska, W. A. Taylor, R. C. Heaton, V. T. Hamilton, R. C. Staroski, and D. R. Phillips, “Isolation and recovery of 82Sr and other spallation products from proton irradiated molybdenum,” American Chemical Society national meeting, 12 1993.
[42] S. Qaim, G. Steyn, I. Spahn, S. Spellerberg, T. van der Walt, and H. Coenen, “Yield and purity of 82Sr produced via the natRb(p,xn)82Sr process,” Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine, vol. 65, pp. 247–52, 02 2007.
[43] T. Ido, “Excitation functions of proton induced nuclear reactions on natRb from 30 to 70 MeV. implication for the production of 82Sr and other medically important Rb and Sr radioisotopes,” Nuclear Instruments and Methods in Physics Research Section B: Beam
Interactions with Materials and Atoms, vol. 194, no. 4, pp. 369–388, 2002
[44] G. Steyn, M. Motetshwane, F. Szelecsényi, and J. Brümmer, “Pairing of thorium with selected primary target materials in tandem configurations: Co-production of 225Ac/213Bi and 230U/226Th generators with a 70 MeV H− cyclotron,” Applied Radiation and Isotopes, vol. 168, p. 109514, 2021.
[45] A. K. H. Robertson et al., “Development of 225Ac Radiopharmaceuticals: TRIUMF Perspectives and Experiences,” Current radiopharmaceuticals, vol. 11, no. 3, pp. 156–172, 2018.
[46] K. Nagatsu, H. Suzuki, M. Fukada, T. Ito, J. Ichinose, Y. Honda, K. Minegishi, T. Higashi, and M.-R. Zhang, “Cyclotron production of 225Ac from an electroplated 226Ra target,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 49, 12 2021.
[47] S. Qaim, F. Tárkányi, and R. Capote, “Nuclear data for the production of therapeutic radionuclides,” IAEA Technical Reports Series, pp. 1–358, 01 2011.
[48] O. R. Pozzi, “Alpha Project: Argentina Project for Developing Production of Ac-225 and Bi-213 and Corresponding Radiopharmaceuticals for Targeted Therapy,” National Atomic Energy Commission (CNEA), Ezeiza Atomic Centre, Argentina, October 2018.
[49] J. Griswold, D. Medvedev, J. Engle, R. Copping, J. Fitzsimmons, V. Radchenko, J. Cooley, M. Fassbender, D. Denton, K. Murphy, A. Owens, E. Birnbaum, K. John, F. Nortier, D. Stracener, L. Heilbronn, L. Mausner, and S. Mirzadeh, “Large scale accelerator production of 225Ac: Effective cross sections for 78–192MeV protons incident on 232Th targets,” Applied Radiation and Isotopes, vol. 118, pp. 366–374, 2016.
[50] C. Duchemin, A. Guertin, F. Haddad, N. Michel, and V. Métivier, “Production of medical isotopes from a thorium target irradiated by light charged particles up to 70 MeV,” Physics in Medicine and Biology, vol. 60, pp. 931–946, 01 2015.
[51] R. Schwarzbach, K. Zimmermann, P. Bläuenstein, A. Smith, and P. August Schubiger, “Development of a simple and selective separation of 67Cu from irradiated zinc for use in antibody labelling: A comparison of methods,” Applied Radiation and Isotopes, vol. 46, no. 5, pp. 329–336, 1995.
[52] J. K. Park, “Measurement of cross sections for proton-induced reactions on natural Zn,” Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, vol. 449, pp. 35–39, 2019.
[53] M. Ayzatskiy, N. Dikiy, A. Dovbnya, Y. Lyashko, V. Nikiforov, B. Shramenko, A. Tenishev, A. Torgovkin, and V. Uvarov, “Comparison of Cu-67 production at cyclotron and electron accelerator,” Proceedings of the 18th International Conference on Cyclotrons and Their Applications, pp. 243–245, 01 2007.
[54] J. Y. Lee, J. Chae, M. G. Hur, S. Yang, Y. Kong, J. Lee, J. Ju, P. Choi, and J. Park, “Theragnostic 64Cu/67Cu Radioisotopes Production With RFT-30 Cyclotron,” Frontiers in Medicine, vol. 9, p. 889640, 05 2022.
[55] S. Ermolaev, B. Zhuikov, V. Kokhanyuk, A. Abramov, N. Togaeva, S. Khamianov, and S. Srivastava, “Production of no-carrier-added 117m Sn from proton irradiated antimony,” Journal of Radioanalytical and Nuclear Chemistry - J RADIOANAL NUCL CHEM, vol. 280, pp. 319–324, 05 2009.
[56] S. Takács, M. Takács, A. Hermanne, F. Tárkányi, and R. Adam Rebeles, “Cross sections of proton induced reactions on natSb,” Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, vol. 297, pp. 44–57, 2013.
[57] M. Aslam, K. Zubia, and S. Qaim, “Nuclear model analysis of excitation functions of αparticle induced reactions on In and Cd up to 60MeV with relevance to the production of high specific activity 117mSn,” Applied Radiation and Isotopes, vol. 132, pp. 181–188,
2018.
[58] M. Mosby, E. Birnbaum, F. Nortier, and J. Engle, “Cross sections for proton-induced reactions on natSb up to 68MeV,” Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, vol. 412, pp. 34–40, 2017.