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ISSN (Print): 1874-4710
ISSN (Online): 1874-4729

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Review Article

Pre-feasibility Study for Establishing Radioisotope and Radiopharmaceutical Production Facilities in Developing Countries

Author(s): Efrain Araujo Perini *, Mikhail Skopchenko, Tran Thu Hong , Rahmat Harianto , Alexis Maître, Maidelys Rosa Rodríguez Rodríguez , Nathalia de Oliveira Santos , Yinglei Guo, Xiangyu Qin , Carlos A. Zeituni and Valeriia N. Starovoitova

Volume 12, Issue 3, 2019

Page: [187 - 200] Pages: 14

DOI: 10.2174/1874471012666190328164253

open access plus

Abstract

Background: A significant number of developing countries have no facilities to produce medical radioisotopes and radiopharmaceuticals.

Objective: In this paper we show that access to life-saving radioisotopes and radiopharmaceuticals and the geographical distribution of corresponding infrastructure is highly unbalanced worldwide.

Methods: We discuss the main issues which need to be addressed in order to establish the production of radioisotopes and radiopharmaceuticals, which are especially important for developing countries as newcomers in the field. The data was gathered from several sources, including databases maintained by the International Atomic Energy Agency (IAEA), World Health Organization (WHO), and other international organizations; personal interactions with representatives in the nuclear medicine field from different regions of the world; and relevant literature.

Results: Developing radioisotope and radiopharmaceutical production program and installing corresponding infrastructure requires significant investments, both man-power and financial. Support already exists to help developing countries establish their medical radioisotope production installations from several organizations, such as IAEA.

Conclusion: This work clearly shows that access to life-saving radioisotopes and the geographical distribution of corresponding infrastructure is highly unbalanced. Technology transfer is important as it not only immediately benefits patients, but also provides employment, economic activity and general prosperity in the region to where the technology transfer is implemented.

Keywords: Radioisotope production, radiopharmaceuticals, developing countries, nuclear medicine, radioisotopes in medical applications, IAEA.

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[1]
United Nations. World Population Prospects 2017.Total Population - Both Sexes. https://esa.un.org/unpd/wpp/Download/ Standard/Population/ [Accessed Sep 12, 2018].
[2]
The International Agency for Research on Cancer (IARC). Global Cancer Observatory: cancer Fact Sheet. Available from. http://gco.iarc.fr/ [Accessed Mar 17, 2019].
[3]
Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 2, 87-108.
[4]
Torre, L.A.; Siegel, R.L.; Ward, E.M.; Jemal, A. Global cancer incidence and mortality rates and trends--an update. Cancer Epidemiol. Biomarkers Prev., 2016, 1, 16-27.
[5]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 10, 21492.
[6]
Dondi, M.; Kashyap, R.; Paez, D.; Pascual, T.; Zaknun, J.; Bastos, F.M.; Pynda, Y. Trends in nuclear medicine in developing countries. J. Nucl. Med., 2011, 2089193
[7]
Paez, D.; Orellana, P.; Gutierrez, C.; Ramirez, R.; Mut, F.; Torres, L. Current status of nuclear medicine practice in latin America and the caribbean. J. Nucl. Med., 2015, 10, 1629-1634.
[8]
Paez, D.; Becic, T.; Bhonsle, U.; Jalilian, A.R.; Nuñez-Miller, R.; Osso, J.A. Current status of nuclear medicine practice in the middle east. Semin. Nucl. Med., 2016, 4, 265-272.
[9]
Brandon, D.; Alazraki, A.; Halkar, R.K.; Alazraki, N.P. The role of single-photon emission computed tomography and SPECT/computed tomography in oncologic imaging. Semin. Oncol., 2011, 1, 87-108.
[10]
Patel, C.N.; Chowdhury, F.U.; Scarsbrook, A.F. Hybrid SPECT/CT: the end of “unclear” medicine. Postgrad. Med. J., 2009, 1009, 606-613.
[11]
Nuclear Technology Development and Economics (NEA). The Supply of Medical Radioisotopes 2018: Medical Isotope Demand and Capacity Projection for the 2018-2023 Period. Available from https://www.oecd-nea.org/cen/docs/2018/sen-hlgmr2018-3.pdf [Accessed Mar 17, 2019].
[12]
Van der Marck, S.C.; Koning, A.J.; Charlton, K.E. The options for the future production of the medical isotope 99 Mo. Eur. J. Nucl. Med. Mol. Imaging, 2010, 1817-1823.
[13]
Derlin, T.; Grünwald, V.; Steinbach, J.; Wester, H-J.; Ross, T.L. Molecular imaging in oncology using positron emission tomography. Dtsch. Arztebl. Int., 2018, 11, 175-181.
[14]
Vaquero, J.J.; Kinahan, P. Positron emission tomographY: Current challenges and opportunities for technological advances in clinical and preclinical imaging systems. Annu. Rev. Biomed. Eng., 2015, 1, 385-414.
[15]
Gholamrezanejhad, A.; Mirpour, S.; Mariani, G. Future of nuclear medicine: SPECT versus PET. J. Nucl. Med., 2009, 7, 16-18.
[16]
Hicks, R.J.; Hofman, M.S. Is There Still a Role for SPECT-CT in Oncology in the PET-CT Era? Nat. Rev. Clin. Oncol., 2012, 12, 712-720.
[17]
Rahmim, A.; Zaidi, H. PET versus SPECT: strengths, limitations and challenges. Nucl. Med. Commun., 2008, 3, 193-207.
[18]
Healy, B.J.; van der Merwe, D.; Christaki, K.E.; Meghzifene, A. Cobalt-60 machines and medical linear accelerators: Competing technologies for external beam radiotherapy. Clin. Oncol., 2017, 2, 110-115.
[19]
International Atomic Energy Agency -Directory of Radiotherapy Center. IAEA DIRAC database. Available from. https://dirac.iaea.org/ [Accessed Jan. 4, 2018].
[20]
World Nuclear Association Radioisotopes in Medicine. http://www.world-nuclear.org/information-library/non-power-nuclear-applications/radioisotopes-research/radioisotopes-in-medicine.aspx [Accessed Jan 4, 2018].
[21]
Souza, C.D.; Zeituni, C.A.; Moura, J.A.; Moura, E.S.; Nagatomi, H.; Feher, A.; Hilario, K.F.; Rostelato, M.E.C.M. Brachytherapy with 125-Iodine sources: transport and radiation protection, INAC - International Nuclear Atlantic Conference, Rio de Janeiro - Brazil. 2009.
[22]
Costa, O.L.; Calvo, W.A.P.; Zeituni, C.A.; Rostelato, M.E.C.M.; Moura, J.A.; Feher, A.; Souza, C.D.; Somessari, S.L. A study about the measurement method of the homogeneity of radioactivity along an iridium-192 wire used in brachytherapy. Nukleonica, 2014, 1(59), 3-6.
[23]
Strom, T.J.; Wilder, R.B.; Fernandez, D.C.; Mellon, E.A.; Saini, A.S.; Hunt, D.C.; Biagioli, M.C. High-dose-rate brachytherapy with or without intensity modulated radiation therapy as salvage treatment for an isolated, gross local recurrence of prostate cancer post-prostatectomy. Brachytherapy, 2014, 2, 123-127.
[24]
Zhang, W.; Li, J.; Li, R.; Zhang, Y.; Han, M.; Ma, W. Efficacy and safety of iodine-125 radioactive seeds brachytherapy for advanced non–small cell lung cancer; A meta-analysis. Brachytherapy, 2018, 2, 439-448.
[25]
Zalutsky, M.R.; Pozzi, O.R. Radioimmunotherapy with alpha-particle emitting radionuclides. Q. J. Nucl. Med. Mol. Imaging, 2004, 4, 289-296.
[26]
Huang, C.Y.; Guatelli, S.; Oborn, B.; Allen, B. SU-E-J-03: A Comprehensive Comparison Between Alpha and Beta Emitters for Cancer Radioimmunotherapy. Med. Phys., 2014, 41(6), 154-155.
[27]
Larson, S.M.; Carrasquillo, J.A.; Cheung, N-K.V.; Press, O.W. Radioimmunotherapy of human tumours. Nat. Rev. Cancer, 2015, 347.
[28]
Al-Tarakji, M.; Feilchenfeldt, J.; Haidar, A.; Szabados, L.; Abdelaziem, S.; Sayed, A.; Toro, A.; Di Carlo, I. Rare occurrence of metastasis from lung cancer to the anus: case report and review of the literature. World J. Surg. Oncol., 2016, 14(1), 157.
[29]
Soliman, D.S.; Fareed, S.; Alkuwari, E.; El-Omri, H.; Al-Sabbagh, A.; Gameel, A.; Yassin, M. Concomitant Classic Hodgkin Lymphoma of Lymph Node and cMYC-Positive Burkitt Leukemia/Lymphoma of the Bone Marrow Presented Concurrently at the Time of Presentation: A Rare Combination of Discordant Lymphomas. Clin. Med. Insights Blood Disord., 2016, 23-28.
[30]
Zahid, R.; Soofi, M.E.; Elmalik, H.; Junejo, K. Primary apocrine carcinoma of the axilla in a male patient: A case report. Clin. Case Rep., 2016, 4, 344-347.
[31]
Kosuda, S. Report on the Current Nuclear Medicine Status of the Asian Member States from the Initial Cooperative Project Meeting (RAS6061/9001/01) of International Atomic Energy Agency/ Regional Cooperative Agreement. Austral-Asian J. Cancer, 2013, 3, 125-128.
[32]
Chen, Y.; Chen, R.; Zhou, X.; Liu, J.; Huang, G. Report on the development and application of PET/CT in mainland China. Oncotarget, 2017, 38, 64417-64426.
[33]
Papash, A.I.; Alenitsky, Y.G. Commercial cyclotrons. Part I: Commercial cyclotrons in the energy range 10-30 MeV for isotope production. Phys. Part. Nucl., 2008, 597-537.
[34]
International Atomic Energy Agency -Directory of Radiotherapy Center. Cyclotron Produced Radionuclides : PhysicalCharacteristics and Production Methods. Available from. https://www-pub.iaea.org/MTCD/Publications/PDF/trs468_web.pdf [Accessed Jan. 4, 2018].
[35]
Saha, G.B.; MacIntyre, W.J.; Go, R.T. Cyclotrons and positron emission tomography radiopharmaceuticals for clinical imaging. Semin. Nucl. Med., 1992, 3, 150-161.
[36]
Schmor, P. Review of Cyclotrons for the Production of Radioactive Isotopes for Medical and Industrial Applications. Rev. Accelerator Sci. Technol., 2011, 1, 103-116.
[37]
Fowler, J.S.; Ido, T. Initial and subsequent approach for the synthesis of 18FDG. Semin. Nucl. Med., 2002, 1, 6-12.
[38]
Yu, S. Review of (18)F-FDG Synthesis and Quality Control. Biomed. Imaging Interv. J., 2006, 4e57
[39]
Knapp, Jr, F.F.; Mirzadeh, S.; Beets, A.L.; Du, M. Production of therapeutic radioisotopes in the ORNL High Flux Isotope Reactor (HFIR), for applications in nuclear medicine, oncology and interventional cardiology, ed.1;. 2005.
[40]
Ehrhardt, G.J.; Ketring, A.R.; Ayers, L.M. Reactor-produced radionuclides at the University of Missouri Research Reactor. Appl. Radiat. Isot., 1998, 4, 295-297.
[41]
Pavshuk, V.; Chuvilin, D. Production of radionuclides - Fission, fragments of nuclear fuel, ed.1. 2005.
[42]
National Research Council. Medical isotope production without highly enriched uranium, ed 1; National Academies Press, 2009.
[43]
Chinol, M.; Cutler, C.S.; Papi, S.; Ketring, A.; Garaboldi, L.; Paganelli, G.; Murray, L. Production of GMP-compliant lutetium-177: radiochemical precursor for targeted cancer therapy. Nucl. Med. Biol., 2010, 6, 717.
[44]
Islami-Rad, S.Z.; Shamsaei, M.; Gholipour-Peyvandi, R.; Ghannadi-Maragheh, M. Reactor production and purification of 153Sm radioisotope via natSm target irradiation. Radiochemistry, 2011, 6, 642-643.
[45]
Banerjee, S.; Ambikalmajan Pillai, M.R.; Ramamoorthy, N. Evolution of Tc-99m in diagnostic radiopharmaceuticals. Semin. Nucl. Med., 2001, 4, 260-277.
[46]
Boschi, A.; Martini, P.; Pasquali, M.; Uccelli, L. Recent achievements in Tc-99m radiopharmaceutical direct production by medical cyclotrons. Drug Dev. Ind. Pharm., 2017, 9, 1402-1412.
[47]
Arino, H.; Thornton, A.; Kramer, H.; Mc, G.J. Production of high purity fission product molybdenum-99., 1971.
[48]
Aliludin, Z.; Mutalib, A.; Sukmana, A. Kadarisman; Gunawan, A.H.; Vandegrift, G.F.; Wu, D.; Srinivasan, B.; Snelgrove, J. Processing of LEU targets for sup 99Mo production -- Demonstration of a modified Cintichem process. Proceedings of the International Meeting on Reduced Enrichment for Research and Test Reactors, Paris France1995.
[49]
Lee, S-K.; Beyer, G.J.; Lee, J.S. Development of Industrial-Scale Fission 99Mo Production Process Using Low Enriched Uranium Target. Nucl. Eng. Technol., 2016, 3, 613-623.
[50]
Sameh, A.; Ache, H.J. Production techniques for fission molybdenum-99. Radiochim. Acta, 1987, 41, 65-72.
[51]
Kotschkov, Y.; Pozdeyev, V.V.; Krascheninnikov, A.I.; Zakharov, N.V. Production of fission 99Mo with closed uranium cycle at the nuclear reactor WWR-Ts. Radiokhimiya, 2012, 54(2), 188-192.
[52]
Stang, Jr, L.G. Manual of isotope production processes in use at Brookhaven National Laboratory, ed 1; Brookhaven National Laboratory: Upton, New York, 1964.
[53]
Brown, L.C. Methods and apparatus for selective gaseous extraction of molybdenum-99 and other fission product radioisotopes. EP2580763A2 2015.
[54]
Pillai, M.R.A.; Dash, A.; Knapp, F.F. Sustained Availability of 99mTc: Possible Paths Forward. J. Nucl. Med., 2013, 2, 313-323.
[55]
Ruth, T.J. The Medical Isotope Crisis: How We Got Here and Where We Are Going. J. Nucl. Med. Technol., 2014, 4, 245-248.
[56]
International Atomic Energy Agency. Licensing Process for Nuclear Installations. Available from. https://www.iaea.org/ publications/8429/licensing-process-for-nuclear-installations [Accessed Jan. 4, 2019].
[57]
Doherty, J.; Graham, D. The Radiopharmacy.In: Practical Nuclear Medicine; Springer London: London, 2005, pp. 113-141.
[58]
International Organization for Standardization. Cleanrooms and associated controlled environments. (ISO 14644-1); ISO, 2015.
[59]
Owunwanne, A.; Patel, M.; Sadek, S. Design of a radiopharmacy, in: The 22 Handbook of Radiopharmaceuticals, ed.1; Springer Boston, MA. 1995.
[60]
International Atomic Energy Agency. Operational guidance on hospital radiopharmacy: a safe and effective approach. Available from. http://www-pub.iaea.org/MTCD/publications/PDF/Pub1342/ Pub1342_web.pdf [Accessed Sept, 18, 2018].
[61]
Campos, F.E.d.; Perini, E.A.; Júnior, C.L.Z.; Aparecido, W.; Calvo, P.; Starovoitova, V.N. Main Steps for Radiopharmaceuticals Hot Cells Validation in Accordance with GMP Requirements: Methodology and Practical Guid. J. Environ. Sci. Eng. A, 2018, 3
[62]
European Association of Nuclear Medicine (EANM)- Radiopharmacy Committee. Guidelines On Current Good Radiopharmacy Practice (Cgrpp) In The Preparation Of Radiopharmaceuticals. https://www.eanm.org/publications/guidelines/gl_radioph_cgrpp.pdf [Accessed Jan. 4, 2019].
[63]
Elsinga, P.; Todde, S. Fau - Penuelas, I.; Penuelas I Fau - Meyer, G.; Meyer G Fau - Farstad, B.; Farstad B Fau - Faivre-Chauvet, A.; Faivre-Chauvet A Fau - Mikolajczak, R.; Mikolajczak R Fau - Westera, G.; Westera G Fau - Gmeiner-Stopar, T.; Gmeiner-Stopar T Fau - Decristoforo, C.; Decristoforo, C. Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. Eur. J. Nucl. Med. Mol. Imaging, 2010, 4, 1049-1062.
[64]
Gnanasegaran, G.; Ballinger, J.R. Molecular imaging agents for SPECT (and SPECT/CT). Eur. J. Nucl. Med. Mol. Imaging, 2014, 1, 013-2643.
[65]
Sharp, S.E.; Trout, A.T.; Weiss, B.D.; Gelfand, M.J. MIBG in neuroblastoma diagnostic imaging and therapy. Radiographics, 2016, 1, 258-278.
[66]
Spanu, A.; Solinas, M.E.; Chessa, F.; Sanna, D.; Nuvoli, S.; Madeddu, G. 131I SPECT/CT in the follow-up of differentiated thyroid carcinoma: incremental value versus planar imaging. J. Nucl. Med., 2009, 2, 184-190.
[67]
Chen, J.J.; LaFrance, N.D.; Allo, M.D.; Cooper, D.S.; Ladenson, P.W. Single photon emission computed tomography of the thyroid. J. Clin. Endocrinol. Metab., 1988, 6, 1240-1246.
[68]
Pandit-Taskar, N.; Batraki, M.; Divgi, C.R. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J. Nucl. Med., 2004, 8, 1358-1365.
[69]
Inai, R.; Shinya, T.; Tada, A.; Sato, S.; Fujiwara, T.; Takeda, K.; Kunisada, T.; Yanai, H.; Ozaki, T.; Kanazawa, S. Diagnostic value of Thallium-201 scintigraphy in differentiating malignant bone tumors from benign bone lesions. Ann. Nucl. Med., 2015, 8, 674-681.
[70]
Ficaro, E.P.; Corbett, J.R. Advances in quantitative perfusion SPECT imaging. J. Nucl. Cardiol., 2004, 1, 62-70.
[71]
Bekerman, C.; Hoffer, P.B.; Bitran, J.D.; Gupta, R.G. Gallium-67 citrate imaging studies of the lung. Semin. Nucl. Med., 1980, 3, 286-301.
[72]
Eberlein, U.; Cremonesi, M.; Lassmann, M. Individualized Dosimetry for Theranostics: Necessary, Nice to Have, or Counterproductive? J. Nucl. Med., 2017(Suppl. 2), 97S-103S.
[73]
MacKay, J.A.; Li, Z. Theranostic agents that co-deliver therapeutic and imaging agents? Adv. Drug Deliv. Rev., 2010, 11, 1003-1004.
[74]
Ahn, B-C. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer, ed 1; , 2016.
[75]
Müller, C.; Domnanich, K.A.; Umbricht, C.A.; van der Meulen, N.P Scandium and terbium radionuclides for radiotheranostics: Current state of development towards clinical application. Br. J. Radiol, , 20180074.
[76]
Rosch, F.; Herzog, H.; Qaim, S.M. The beginning and development of the theranostic approach in nuclear medicine, as exemplified by the radionuclide pair (86)Y and (90)Y. Pharmaceuticals (Basel), 2017, 10(2)pii E56
[77]
Abram, U.; Alberto, R. Technetium and rhenium: Coordination chemistry and nuclear medical applications. J. Br. Chem. Soc, 2006.1486-1500
[78]
Hjelstuen, O.K. Technetium-99m chelators in nuclear medicine. A review. Analyst, 1995, 3, 863-866.
[79]
Rösch, F.; Knapp, F.F. Radionuclide Generators.Handbook of Nuclear Chemistry; Springer US: Boston, MA, 2011, pp. 1935-1976.
[80]
Chatal, J.F.; Rouzet, F.; Haddad, F.; Bourdeau, C.; Mathieu, C.; Le Guludec, D. Story of Rubidium-82 and Advantages for Myocardial Perfusion PET Imaging. Front. Med., 2015, 65.
[81]
Rösch, F. 68Ge/68Ga Generators: Past, Present, and Future, Berlin, Heidelberg. 2013, 3, 16.
[82]
Padhy, A.K.; Dondi, M. Thematic planning: The role of the international atomic energy agency in promoting education, medical research, and technology transfer among nuclear medicine communities of developing countries. Semin. Nucl. Med., 2008, 2, S2-S4.
[83]
International Atomic Energy Agency. Human Health Campus: Resources and Learning for Health Professionals. Available from. https://humanhealth.iaea.org/hhw/ [Accessed Sept, 18, 2019].
[84]
World Nuclear University - School on Radiation Technology. Training the nuclear industry's best. Available from. https://www.world-nuclear-university.org [Accessed Mar. 4, 2019].

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