In nuclear medicine radionuclides are used for a variety of useful applications, such as diagnosis, therapy, prevention of many serious ailments and research to evaluate metabolic, physiologic and pathologic conditions of the human body. The successful production and usage of these radionuclides extends to oncology, cardiology and even psychiatry by imaging procedures where information about the function of every major organ/ tissue of the human body can be generated. A large number of radionuclides used in nuclear medicine are produced in cyclotrons, accelerators or in nuclear reactors, and production is an important and constantly evolving issue. In addition to this different radionuclides play significant roles in technological applications of importance to our daily life as well for scientific research [1,2]. Production cross sections for charged particles especially nuclear reactions on metals which are induced by protons are important in medical radioisotopes production [3,4]. To optimize the production routes, the charged particle induced cross-sections are desired. For the optimization of the radioisotope produced, a full knowledge of the excitation function is necessary, which helps to maximize the yield of the desired product and to minimize the radioactive impurities . At present the Positron Emission Tomography (PET) imaging technique is widely used for planning, early diagnosis of cancer and evaluation of the treatment response in patients with cancer, this imaging technique is used to studies diseases of heart, brain, thyroid etc. . For a variety of the radioisotopes used in the PET technique, the excitation functions of proton induced by nuclear reactions were calculated using a Monte Carlo nuclear reaction simulation code TALYS 1.6 . The obtained results were compared with the experimental data existing in the EXFOR .
2 Software and methods
Nuclear medicine uses a trace amount of radioactive substances called radiotracers that are typically injected into the bloodstream, inhaled or swallowed to provide diagnostic information that gives accurate and immediate diagnosis regarding the functioning of a specific organ in the human body or to treat a disease. It is used to form images of the bones, thyroid, liver, heart, and many other organs and also helps in treating diseased organs and certain types of cancer tumours.
Calculations based on nuclear reaction models play an important role in the development of reaction cross sections . In this work the excitation Function calculations were carried out with nuclear reaction simulation code TALYS1.6. TALYS is a Monte Carlo code. TALYS was initially develpoed in 1998, when it was decided to implement the combined knowledge of nuclear reactions into one single software package which integrates the pre-equilibrium, direct, optical model, statistical and fission nuclear reaction models and for all the open reaction channels it gives prediction in one calculation scheme.
The TALYS code is a nuclear reaction computer program which simulates basically all types of nuclear reactions, it runs on Linux operation system and is written in the FORTRAN programming language. One of the possible outcomes of using a Monte Carlo method for nuclear data evaluation is that a series of correlations can be extracted from the previous results. The objective and vision of its construction was to provide a complete and accurate simulation of nuclear reactions that involve neutrons, photons, protons, deuterons, tritons, 3He, and alpha particles in the 1 keV-200 MeV energy range, with some exceptions. The code’s data was based on the reference input parameter library through an optimal combination of reliable nuclear models, resilience and ease of use [7,9].
The theory of excitation functions for production of medical radioisotopes are obtained with proton induced reactions (p,2n) for some radioisotopes used in medicine that are important for the development of improved nuclear reaction theory and for many medical applications were calculated by use TALYS 1.6 code. The calculation for nuclear reactions, are usually employed in cases where there is a shortage of experimental data or there are other controversies. Moreover, it ensures the internal consistency of the data, and also allows us to predict and extrapolate the experimental data .
Ethical approval: The conducted research is not related to either human or animals use.
3 Result and Discussions
Excitation functions via proton induced reactions are important for many medical applications and for development of improved nuclear reaction theory. In the present work, the calculated excitation functions for production of medical radioisotopes with proton induced nuclear reactions 56Fe(p,2n)55Co, 58Fe(p,2n)57Co, 111Cd(p,2n)110In, 112Cd(p,2n)111In, 125Te(p,2n)124I, 126Te(p,2n)125I, 68Zn(p,2n)67Ga are carried out using Monte Carlo simulation code TALYS 1.6. The calculated results are shown in Figures 1-7 together with the experimental data existing in the EXFOR library. Additionally, the half-life, and decay data of produced radioisotopes in this study are shown in Table 1, as well as the calculated the threshold energy (E-threshold) and the Q-value of the reactions calculated by the TALYS code.
3.1 Cobalt Radioisotopes Production
55Co and 57Co are two important radioisotopes of cobalt. The first one is used in Positron Emission Tomography (PET) to detect of cancer and other diseases such as cardiac and cerebral disease. In the late 1990s the most important application of 55Co was developed, in the field of imaging neuronal damage from a stroke or traumatic injury. 57Co is applied in various studies as a radioactive tracer. 57Co with Vitamin B 12 (albumin) labeled is used in diagnostic kits to study anemia, 57Co is a useful Mossbauer radioisotope, its use as a calibration standard for gamma-spectrometers and single photon emission tomography (SPECT) are its most general use. It is also used in medicine to help detect cancerous tumors and as a component in medical equipment studying the chemical properties of various materials or testing the response of Gamma cameras [12,13,14,15]. By using TALYS 1.6 code, the excitation function of proton-induced were calculated for the reactions 56Fe(p,2n)55Co, 58Fe(p,2n)57Co and compared with the available experimental data in EXFOR library as shown in Figures 1 and 2 at proton energies up to 50 MeV. As noted the best energy range for production is from 18 to 35 MeV and from 14 to 28 MeV for produced radioisotopes 55Co and 57Co respectively.
3.2 Indium Radioisotopes Production
110In and 111In are indium’s radioisotopes used in specialized diagnostic applications, e.g. brain studies, infection and colon transit studies. They are used as a radioactive tracer in nuclear medicine in a chelate form, as a cerebrospinal fluid tracer. It also used as a white blood cell labeling agent (also called indium-111 white blood cell scan) and as an antibody label. Indium-111 oxine is also useful for labelling blood cell components. Other applications like labelling of platelets for thrombus detection and labelled leukocytes for localization of the inflammation, also leukocyte kinetics. Used with Ga-67 for soft tissue infection detection and osteomyelitis detection, white blood cell imaging (also called indium-111 white blood cell scan), cellular dosimetry, myocardial scans, treatment of leukemia, imaging tumors [20,21,22,23,24]. Excitation functions of the proton-induced at energies up to 50 MeV activities on 111Cd and 112Cd via the two reactions 111Cd(p,2n)110In, 112Cd(p,2n)111In were calculated by TALYS 1.6 code to obtained radioisotopes 110In and 111In respectively, the comparison of experimental and calculated results of reactions 111Cd(p,2n)110In, 112Cd(p,2n)111In are represented in Figures 3 and 4. The best production range for each of 110In and 111In is 12–30 MeV.
3.3 Iodine Radioisotopes Production
124I is the only long-life positron emitter isotope of iodine, which can be used both for diagnosis and therapy and remains the most frequently used radionuclides for thyroid imaging. 124I used in PET applications and it is attracting increasing interest for long-term clinical studies. With availability high quality of PET technology there is role in thyroid cancer imaging, as well as promising applications in neurology and oncology. Because of 124I long half -life (4.18 d), stability, and radiation emissions, this permitted to use in several applications in oncological and nononcological fields.
125I is a low energy gamma emitter, it can be used for a variety of applications. 125I is a versatile isotope that is becoming more diffuse in diagnostic and therapeutic applications. It is also included in in-vitro diagnostic kits (radioimmunoassay), as a source for bone densitometry devices and therapeutic seed used in prostate cancer treatment. It is used in radiation therapy to treat brain tumors, Lung Cancer, uveal melanomas, Eye Plaques [10,32,33,34]. To discuss the theoretical calculated results of the excitation functions of two iodine radioisotopes 124I and 125I mentioned above, via 125Te(p,2n)124I, 126Te(p,2n)125I reactions, we present Figures 5 and 6 that show the comparison of the current calculated results for the excitation functions by using TALYS 1.6 with the experimental data from EXFOR library. The energy range of proton was selected between 10 and 90 MeV in Figure 5 for 125Te(p,2n)124I reaction and between 10 and 100 in Figure 6 126Te(p,2n)125I reaction to make a comparison with the experimental data reported in the literature. The most appropriate production range for 124I and 125I using 125Te(p,2n)124I, 126Te(p,2n)125I nuclear reaction is 12–30 MeV.
3.4 Gallium Radioisotope Production
67Ga is used to find and treat certain diseases or to study the function of the body’s organs. 67Ga used in the imaging of lymphoma tumours, useful for detection of inflammatory disease especially of soft tissue, and sites of inflammation such as chronic infections and abscess. and also septic arthritis, and cellulitis, spinal osteomyelitis, ulcerative colitis, interstitial nephritis, in addition to localization of source of fever in cases of fever of unknown origin (FUO) and other diseases.
Localization of inflammatory foci in postoperative patients considered as one of the most uses of 67Ga, also in patients who present with fever of undetermined origin. On the other hand, Gallium-67 citrate is used to detect types of cancer such as Hodgkin’s disease, lymphoma, bronchial carcinoma and lung cancer. Excitation functions of the proton-induced at energies up to 100 MeV activities on 68Zn via reaction 68Zn(p,2n)67Ga were calculated by TALYS 1.6 code to obtained radioisotopes 67Ga [37,38,39,40] The calculated and experimental excitation function of 68Zn(p,2n)67Ga reaction have been plotted in Figure 7. The most appropriate production range for 67Ga using 68Zn(p,2n)67Ga nuclear reaction is 12–28 MeV.
4 Standard Deviation
Standard deviation is the measure of spread in the statistics of a set of data from its mean. For the excitation function obtained in the current work for the radioisotopes used in nuclear medicine, 55Co, 57Co, 110In, 111In, 124I, 125I and 67Ga via proton induced, the standard deviation were calculated by using the formula:
Where x is one of value of data, x is the average of all values in data, n is the number of values in the data. The results of the Standard deviation are listed in Table 2.
In this work, the calculated excitation functions of 56Fe(p,2n)55Co, 58Fe(p,2n)57Co, 111Cd(p,2n)110In, 112Cd(p,2n)111In, 125Te(p,2n)124I, 126Te(p,2n)125I, 68Zn(p,2n)67Ga reactions have been carried out using nuclear reaction model TALYS 1.6. The calculations are in a good agreement with the experimental results, which were all were taken from the EXFOR library, except as seen in Figure 7, some of the experimental data is higher in the peaked region by about 25%, this could be due to the older experimental technique used in this measurement. The resulting radioisotopes 55Co, 57Co, 110In, 111In, 124I, 125I and 67Ga have important and wide applications in nuclear medicine, and according to the results were shown in Figures 1-7 the small extent of energy so it can be produced by small sized cyclotrons.
Aydin, A., Şarer, B., Tel, E., New calculation of excitation functions of proton-induced reactions in some medical isotopes of Cu, Zn and Ga, Applied Radiation and Isotopes, 2007, 65, 365-370. Web of ScienceCrossrefGoogle Scholar
Kilinç, F., Karpuz, N., Çetin, B., Calculation of the (p, n) Reaction Cross Section of Radionuclides Used for PET Applications, Acta Physica Polonica A, 2016, 130(1), 318-319. CrossrefWeb of ScienceGoogle Scholar
Karpuz Demir, N., Çetin, B., Akkurt, i., Noori, S.S., Calculations of Double Differential Cross Sections on 56Fe, 63Cu and 90Zr Neutron Emission in Proton Induced Reactions, Acta Physica Polonica A, 2017, 132(3-II), 1181-1185. CrossrefGoogle Scholar
Mohamed, M. B., Study of the excitation function for some cyclotron produced radionuclides, PhD thesis, Mansoura University, Egypt, 2006. Google Scholar
IAEA, Production of Long Lived Parent Radionuclides for Generators: 68Ge, 82Sr, 90Sr and 188W, IAEA radioisotopes and radiopharmaceuticals series No. 2, 2010, STI/PUB/1436, VIENNA. Google Scholar
Noori, S. S., Akkurt, i., Karpuz, N., Comparison of Excitation Functions of Longer and Shorter Lived Radionuclides, Acta Physica Polonica A, 2017, 132 (3-II), 1186-1188. Web of ScienceCrossrefGoogle Scholar
Koning, A., Hilaire, S., Goriely, S., TALYS-1.6 A Nuclear Reaction Program, User Manual, 2013, NRG, the Netherlands. Google Scholar
EXFOR/CSISRS, Experimental Nuclear Reaction Data File, 2017, Brookhaven National Laboratory, National Nuclear Data Center. Google Scholar
Issa, S. A. A. M., Cross Section for Residual Nuclide Production by Proton–Induced Reaction with Heavy Target Elements at Medium Energies, PhD thesis, Al-Azhar University, Assiut, Egypt, 2009. Google Scholar
Artun, O., Aytekin, H., Calculation of excitation functions of proton, alpha and deuteron induced reactions for production of medical radioisotopes 122-125I, Nuclear Instruments and Methods in Physics Research B, 2015, 345, 1-8. CrossrefGoogle Scholar
IAEA, Cyclotron Produced Radionuclides: Physical Characteristics and Production Methods Technical, Technical Reports Series No. 468, 2009, STI/DOC/010/468, Vienna, Austria. Google Scholar
Spellerberg, S., Reimer, P., Blessing, G., Coenen, H. H., Qaim, S. M., Production of 55Co and 57Co via Proton Induced Reactions on Highly Enriched 58Ni, Applied Radiation and Isotopes, 1998, 49(12), 1519-1522. CrossrefGoogle Scholar
Mirzaii, M., Kakavand, T., Talebi, M., Rajabifar, S., Electrodeposition iron target for the cyclotron production of 55Co in labeling proteins, Journal of Radioanalytical and Nuclear Chemistry, 2012, 292(1), 261-267. CrossrefGoogle Scholar
Usman, A. R., Khandaker, M. U., Haba, H., Murakami, M., Otuka, N., Measurements of deuteron-induced reaction crosssections on natural nickel up to 24 MeV, Nuclear Instruments and Methods in Physics Research B, 2016, 368, 112–119. CrossrefGoogle Scholar
Mastren, T., Marquez, B. V., Sultan, D. E., Bollinger, E., Eisenbeis, P., Voller, T., Lapi, S. E., Cyclotron production of high specific activity 55Co and in vivo evaluation of the stability of 55Co metal-chelate-peptide complexes, HHS Public Access, Author manuscript, 2015, 14, 526–533. Google Scholar
Wenron, Z., Hanlin, L., Weixiang, Y., Measurement of cross sections by bombarding Fe with protons up to 19 MeV, Chinese Journal of Nuclear Physics, 1993, 15(4), 337-340.Google Scholar
Levkovski, V. N., Cross sections of medium mass nuclide activation (A=40-100) by medium energy protons and alpha-particles (E=10-50 MeV), Book: Act. Cs. By Protons and Alphas, Moscow, 1991.Google Scholar
Lagunas-Solar, M. C., Jungerman, J. A., Cyclotron Production of Carrier-Free Cobalt-55, a New Positron Emitting Label for Bleomycin, The International Journal of Applied Radiation and Isotopes, 1979, 30, 25-32.CrossrefGoogle Scholar
Fakhari, F. E., Separation and Purification of 111In from Irradiated Cadmium Targets by Solid Phase Extraction (SPE) Method for Medical Applications, PhD thesis, Philipps-University Marburg, The Department of Chemistry, 2006. Google Scholar
Mostafa, M., El-Sadek, A. A., El-Said, H., El-Amir, M. A., 99Mo/ 99mTc–113Sn/113mIn Dual Radioisotope Generator Based on 6-Tungstocerate(IV) Column Matrix, Journal of Nuclear and Radiochemical Sciences, 2009, 10(1), 1-12. Google Scholar
Al-Abyad, M., Proton induced nuclear reactions on cadmium up 17 MeV, Third International Conference on Radiation Sciences and Applications (12 - 16 November 2012, Hurghada, Egypt) Cairo 13759, Egypt, 2012, 353-363. Google Scholar
Khandaker, M. U., Kim, K., Lee, M., Kim, K. S., Lee, Y. S., Cho, Y. O., Lee, Y. O., Kim, G., Experimental Study of Proton Induced Cross-sections on Natural Cadmium Leading to the Production of 111In Radionuclide, Journal of Nuclear Science and Technology, 2008, 45, 237–240. CrossrefGoogle Scholar
Kilinç, F., Karpuz, N., Çetina, B., Theoretical Cross-Section Calculation of In-111, Tc-99m, Co-57 Radioisotopes Used for Kidney Imaging, Acta Physica Polonica A, 2016, 130(1), 311-312. Web of ScienceCrossrefGoogle Scholar
Marten, M., Schuring, A., Scobel, W., Probst, H. J., Preequilibrium Neutron Emission in 109Ag(3He,xn) and 111Cd(p,xn) Reactions, Zeitschrift für Physik A Atoms and Nuclei, 1985, 322(1), 93-103.CrossrefGoogle Scholar
Skakun, E. A., Klyucharev, A. P., Rakivnenko, Y. N., Romanii, I. A., Excitation Functions of (p,n)- and (p,2n)-Reactions on Cadmium Isotopes, Izvestiya Akademii Nauk SSSR, Seriya Fizicheskaya, 1975, 39(1), 24-30.Google Scholar
Hermanne, A., Adam-Rebeles, R., Van den Winkel, P., Tarkanyi, F., Takacs, S., Production of 111In and 114mIn by proton induced reactions: an update on excitation functions, chemical separation - purification and recovery of target material, Radiochimica Acta, 2014, 102(12), 1111-1126.Google Scholar
Tárkányi, F., Szelecsényi, F., Kopecký, P., Molnár, T., Andó, L., Mikecz, P., Tóth, GY., Rydl, A., Cross Sections of Proton Induced Nuclear Reactions on Enriched 111Cd and 112Cd for the Production of 111In for Use in Nuclear Medicine, Applied Radiation and Isotopes, 1994, 45(2), 239-249.CrossrefGoogle Scholar
Otozai, K., Kume, S., Mito, A., Okamura, H., Tsujino, R., Kanchiku, Y., Katoh, T., Gotoh, H., Excitation Functions for the Reactions Induced by Protons on Cd up to 37 MeV, Nuclear Physics, 1966, 80(2), 335-348.CrossrefGoogle Scholar
Takács, S., Tárkányi, F., Hermanne, A., Validation and upgrading of the recommended cross-section data of charged particle reactions: Gamma emitter radioisotopes, Nuclear Instruments and Methods in Physics Research Section B, 2005, 240(4), 790-802.CrossrefGoogle Scholar
Cascini, G. L., Asabella, A. N., Notaristefano, A., Restuccia, A., Ferrari, C., Rubini, D., Altini, C., Rubini, G., 124Iodine: A Longer-Life Positron Emitter Isotope—NewOpportunities in Molecular Imaging, Hindawi Publishing Corporation, BioMed Research International, 2014, 2014(1), 1-7. Google Scholar
Demir, B., Çapali, V., Sarpün, i. H., Kaplan, A., Production Cross–Section Calculations of Medical125I Radionuclide Using α, d and γ Induced Reactions, SDU Journal of Science (E-Journal), 2015, 10, 116-121. Google Scholar
Hohn, A., Nortier, F. M., Scholten, B., van der Walt, T. N., Coenen, H. H., Qaim, S. M., Excitation Functions of 125Te(p,xn)-Reactions from Their Respective Thresholds up to 100 MeV with Special Reference to the Production of 124I, Applied Radiation and Isotopes, 2001, 55, 149-156.CrossrefGoogle Scholar
Scholten, B., Hassan, K .F., Saleh, Z. A., Coenen, H. H., Qaim, S. M., Comparative studies on the production of the medically important radionuclide 124I via p-, d-, 3He- and α-particle induced reactions, Conference on Nuclear Data for Science and Technology, 2007, 2, 1359-1361.Google Scholar
Morton, K. A., Jarboe, J., Burke, E. M., Gallium-67 Imaging in Lymphoma: Tricks of the Trade, Journal Nuclear Medicine Technology, 2000, 28(4), 221-232. Google Scholar
Avagyan, R., Avetisyan, R., Bazoyan, G., Hakobyan, M., Kerobyan, I., Estimation of the Productivity Isotope 67Ga on Cyclotron C18 for Nuclear Medicine, Universal Journal of Applied Science, 2014, 2(7), 221-224. Google Scholar
Nasrabadi, M. N., Sepiani, M., Study of components and statistical reaction mechanism in simulation of nuclear process for optimized production of 64Cu and 67Ga medical radioisotopes using TALYS, EMPIRE and LISE++ nuclear reaction and evaporation codes, American Institute of Physics, 2015, AIP Conference Proceedings 1653, 020076-1-020076-6. Google Scholar
Szelecsenyi, F., Kovacs, Z., Nagatsu, K., Fukumura, K., Suzuki, K., Mukai, K., Investigation of direct production of 68Ga with low energy multiparticle accelerator, Radiochimica Acta, 2012, 100(1), 5-11.CrossrefGoogle Scholar
Szelecsenyi, F., Steyn, G. F., Kovacs, Z., Van der Walt, T. N., Suzuki, K., Okada, K., Mukai, K., New cross-section data for the 66Zn(p,n)66Ga, 68Zn(p,3n)66Ga, natZn(p,x)66Ga, 68Zn(p,2n)67Ga and natZn(p,x)67Ga nuclear reactions up to 100 MeV, Nuclear Instruments and Methods in Physics Research Section B, 2005, 234(4), 375-386.CrossrefGoogle Scholar
Stoll, T., Kastleiner, S., Shubin, Yu. N., Coenen, H. H., Qaim, S. M., Excitation functions of proton induced reactions on 68Zn from threshold up to 71 MeV, with specific reference to the production of 67Cu, Radiochimica Acta, 2002, 90(6), 309-313.Google Scholar
Hermanne, A., Szelecsenyi, F., Sonck, M., Takacs, S., Tarkanyi, F., Van den Winkel, P., New Cross Section Data on 68Zn(p,2n)67Ga and natZn(p,xn)67Ga Nuclear Reactions for the Development of a reference data base, Journal of Radioanalytical and Nuclear Chemistry, 1999, 240(2), 623-630.CrossrefGoogle Scholar
Szelecsenyi, F., Boothe, T. E., Takacs, S., F. Tarkanyi, E. Tavano, Evaluated cross section and thick target yield data bases of Zn + p processes for practical applications, Applied Radiation and Isotopes, 1998, 49(8), 1005-1032.CrossrefGoogle Scholar
Szelecsenyi, F., Boothe, T. E., Tavano, E., Plitnikas, M. E., Feijoo, Y., Takacs, S., Tarkanyi, F., Szucs, Z., New cross section data for 66-67-68Zn+p reactions up to 26 MeV, Nuclear Data for Science and Technology, Gatlinburg 1994, 393.Google Scholar
Hermanne, A., Walravens, N., Cicchelli, O., Optimization of isotope production by cross section determination, Nuclear Data for Science and Technology, Juelich 1991, 616-618.Google Scholar
Tarkanyi, F., Szelecsenyi, F., Kovacs, Z., Sudar, S., Excitation functions of proton induced nuclear reactions on enriched 66Zn,67Zn and 68Zn production of 67Ga and 66Ga, Radiochimica Acta, 1990, 50(1-2), 19-26.Google Scholar
Little, F. E., Lagunas-Solar, M.C., Cyclotron production of 67Ga. cross sections and thick-target yields for the 67Zn(p,n) and 68Zn(p,2n) reactions, The International Journal of Applied Radiation and Isotopes, 1983, 34(3), 631-637.CrossrefGoogle Scholar
Takacs, S., Tarkanyi, F., Hermanne, A., Validation and upgrading of the recommended cross-section data of charged particle reactions: Gamma emitter radioisotopes, Nuclear Instruments and Methods in Physics Research Section B, 2005, 240(4), 790-802.CrossrefGoogle Scholar
About the article
Published Online: 2018-08-20
Conflict of interest: Authors state no conflict of interest.
Citation Information: Open Chemistry, Volume 16, Issue 1, Pages 810–816, ISSN (Online) 2391-5420, DOI: https://doi.org/10.1515/chem-2018-0085.
© 2018 Susan Shukur Noori, İskender Akkurt, Nurdan Karpuz Demir, published by De Gruyter. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License. BY-NC-ND 4.0