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Special radionuclide production activities – recent developments at QST and throughout Japan

  • Kotaro Nagatsu EMAIL logo , Tomoyuki Ohya , Honoka Obata , Kazutoshi Suzuki and Ming-Rong Zhang
Published/Copyright: April 21, 2022
Radiochimica Acta
From the journal Radiochimica Acta Volume 110 Issue 6-9

Abstract

National Institutes for Quantum Science and Technology (QST), formerly known as the National Institute of Radiological Sciences (NIRS), has been engaged in work on radiopharmaceutical science using cyclotrons since 1974. Eight pioneering researchers founded the basis of this field of research at NIRS, and to the present, many researchers and technicians have accumulated both scientific and technical achievements, as well as inherited the spirit of research. Besides, in recent years, we have developed production systems with AVF-930 cyclotron for various ‘non-standard’ radioisotopes applied in both diagnosis and therapy. Here, we review the past 50 years of our activities on radioisotope and radiopharmaceutical development, as well as more recent activities.

Keywords: cyclotron; NIRS; QST; radioisotope production; radiopharmaceuticals
Corresponding author: Kotaro Nagatsu, Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Sciences (iQMS), National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan, E-mail:

Acknowledgements

The authors are grateful to the past and present members of the Department of Advanced Nuclear Medicine, as well as to all who have supported our activities over our half-century-long history. All our achievements are due to the excellent beams provided by the AVF-930 and HM-18 under the operation of our trusted cyclotron crews.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

1. Fukuda, N., Tateno, Y., Rikitake, T., Matsumoto, T., Tomitani, T., Suzuki, K., Koen, H., Musha, H., Okuda, K. Coincidence positron imaging of the liver and heart following rectal administration of 13N-ammonia in liver cirrhosis. Radioisotopes 1977, 26, 872–875; https://doi.org/10.3769/radioisotopes.26.12_872.Search in Google Scholar

2. Kashida, Y., Suzuki, K., Iwata, R., Yoshikawa, K., Tamate, K. Safety handling for cyclotron production of radiopharmaceuticals. J. Label. Compd. 1977, 13, 192.Search in Google Scholar

3. Ido, T., Wan, C-N., Casella, V., Fowler, J. S., Wolf, A. P., Reivich, M., Kuhl, D. E. Labeled 2-deoxy-D-glucose analogs. 18F-labeled 2-deoxy-2-fluoro-D-glucose, 2-deoxy-2-fluoro-D-mannose and 14C-2-deoxy-2-fluoro-D-glucose. J. Label. Compd. Radiopharm. 1977, 14, 175–183.10.1002/jlcr.2580140204Search in Google Scholar

4. Ido, T., Wan, C-N., Fowler, J. S., Wolf, A. P. Fluorination with F2. A convenient synthesis of 2-deoxy-2-fluoro-D-glucose. J. Org. Chem. 1977, 42, 2341–2342; https://doi.org/10.1021/jo00433a037.Search in Google Scholar

5. Reivich, M., Kuhl, D., Wolf, A., Greenberg, J., Phelps, M., Ido, T., Casella, V., Fowler, J., Hoffman, E., Alavi, A., Som, P., Sokoloff, L. The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ. Res. 1979, 44, 127–137; https://doi.org/10.1161/01.res.44.1.127.Search in Google Scholar

6. Hamacher, K., Coenen, H. H., Stöcklin, G. Efficient stereospecific synthesis of nocarrier-added 2-[18F]-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution. J. Nucl. Med. 1986, 27, 235–238.Search in Google Scholar

7. Suzuki, K. A central system for the simultaneous control of several equipments in the preparation of radiopharmaceuticals. In Radiopharmaceuticals and Labelled Compounds, 1985; VIENNA: IAEA-CN-45/63, 1984; pp. 67–75.Search in Google Scholar

8. Comar, D., Berger, G., Crouzel, C., Godot, J. M., Mazière, M., Mestelan, G. Carbon 11 labelled radiopharmaceuticals for brain receptor studies. J. Label. Compd. Radiopharm. 1981, 18, 3–4.10.1002/jlcr.2580181111Search in Google Scholar

9. Lapi, S. E., Welch, M. J. A historical perspective on the specific activity of radiopharmaceuticals: what have we learned in the 35 years of the ISRC? Nucl. Med. Biol. 2013, 40, 314–320; https://doi.org/10.1016/j.nucmedbio.2012.12.010.Search in Google Scholar

10. Suzuki, K., Inoue, O., Hasimoto, K., Yamasaki, T., Kuchiki, M., Tamate, K. Computer-controlled large scale production of high specific activity C-11- Ro 15-1788 for PET studies of benzodiazepine receptors. Int. J. Appl. Radiat. Isot. 1985, 36, 971–976; https://doi.org/10.1016/0020-708x(85)90258-3.Search in Google Scholar

11. Crouzel, C., Långström, B., Pike, V. W., Coenen, H. H. Recommendations for a practical production of [11C]methyl iodide. Appl. Radiat. Isot. 1987, 38, 601–603; https://doi.org/10.1016/0883-2889(87)90123-7.Search in Google Scholar

12. Hashimoto, K., Inoue, O., Goromaru, T., Yamasaki, T. Changes in in vivo binding of 3H-RO 15-1788 in mouse brain by reserpine. Nucl. Med. Biol. 1988, 15, 637–644; https://doi.org/10.1016/0883-2897(88)90055-4.Search in Google Scholar

13. Shinotoh, H., Yamasaki, T., Inoue, O., Itoh, T., Suzuki, K., Hashimoto, K., Tateno, Y., Ikehira, H. Visualization of specific binding sites of benzodiazepine in human brain. J. Nucl. Med. 1986, 27, 1593–1599.Search in Google Scholar

14. Shinotoh, H., Iyo, M., Yamada, T., Inoue, O., Suzuki, K., Itoh, T., Fukuda, H., Yamasaki, T., Tateno, Y., Hirayama, K. Detection of benzodiazepine receptor occupancy in the human-brain by positron emission tomography. Psychopharmacology 1989, 99, 202–207; https://doi.org/10.1007/bf00442808.Search in Google Scholar

15. Stöcklin, G., Pike, V. W., Eds. Radiopharmaceuticals for Positron Emission Tomography – Methodological Aspects; The Netherland: Dordrecht, 1993.10.1007/978-94-015-8204-9Search in Google Scholar

16. Suzuki, K., Inoue, O., Tamate, K., Mikado, F. Production of 3-N-[11C]methylspiperone with high specific activity and high radiochemical purity for PET studies – suppression of its radiolysis. Appl. Radiat. Isot. 1990, 41, 593–599; https://doi.org/10.1016/0883-2889(90)90046-j.Search in Google Scholar

17. Suzuki, K. Development of a multipurpose equipment for the repeated syntheses of 11C labeled alkyl iodides with high specific activity. Radiochim. Acta 1990, 50, 49–53; https://doi.org/10.1524/ract.1990.50.12.49.Search in Google Scholar

18. Inoue, O., Suhara, T., Itoh, T., Kobayashi, K., Suzuki, K., Tateno, Y. In vivo binding of [11C]Ro15-4513 in human brain measured with PET. Neurosci. Lett. 1992, 145, 133–136; https://doi.org/10.1016/0304-3940(92)90004-q.Search in Google Scholar

19. Suhara, T., Fukuda, H., Inoue, O., Itoh, T., Suzuki, K., Yamasaki, T., Tateno, Y. Age-related changes in human D1 dopamine receptors measured by positron emission tomography. Psychopharmacology 1991, 103, 41–45; https://doi.org/10.1007/bf02244071.Search in Google Scholar

20. Shinotoh, H., Inoue, O., Hirayama, K., Aotsuka, A., Asahina, M., Suhara, T., Yamazaki, T., Tateno, Y. Dopamine D1 receptors in Parkinson’s disease and striatonigral degeneration: a positron emission tomography study. J. Neurol. Neurosurg. Psychiatry 1993, 56, 467–472.https://doi.org/10.1136/jnnp.56.5.467.Search in Google Scholar

21. Iyo, M., Namba, H., Fukushi, K., Shinotoh, H., Nagatsuka, S., Suhara, T., Sudo, Y., Suzuki, K., Irie, T. Measurement of acetylcholinesterase by positron emission tomography in the brains of healthy controls and patients with Alzheimer’s disease. Lancet 1997, 349, 1805–1809; https://doi.org/10.1016/s0140-6736(96)09124-6.Search in Google Scholar

22. Maeda, J., Suhara, T., Ogawa, M., Okauchi, T., Kawabe, K., Zhang, M-R., Semba, J., Suzuki, K. In vivo binding properties of [Carbonyl-11C]WAY-100635: effect of endogenous serotonin. Synapse 2001, 40, 122–129; https://doi.org/10.1002/syn.1033.Search in Google Scholar

23. Irie, T., Fukushi, K., Akimoto, Y., Tamagami, H., Nozaki, T. Design and evaluation of radioactive acetylcholine analogs for mapping brain acetylcholinesterase (AchE) in vivo. Nucl. Med. Biol. 1994, 21, 801–808; https://doi.org/10.1016/0969-8051(94)90159-7.Search in Google Scholar

24. Irie, T., Fukushi, K., Namba, N., Iyo, M., Tamagami, H., Nagatsuka, S., Ikota, N. Brain acetylcholinesterase activity: validation of a PET tracer in a rat model of Alzheimer’s disease. J. Nucl. Med. 1996, 37, 649–665.Search in Google Scholar

25. Noguchi, J., Suzuki, K. Automated synthesis of the ultra high specific activity of [11C]Ro15-4513 and its application in an extremely low concentration region to an ARG study. Nucl. Med. Biol. 2003, 30, 335–343; https://doi.org/10.1016/s0969-8051(02)00422-5.Search in Google Scholar

26. Larsen, P., Ulin, J., Dahlatron, K., Jensen, M. Synthesis of [11C]iodomethane by iodination of [11C]methane. Appl. Radiat. Isot. 1997, 48, 153–157; https://doi.org/10.1016/s0969-8043(96)00177-7.Search in Google Scholar

27. Zhang, M. R., Suzuki, K. Sources of carbon which decrease the specific activity of [11C]CH3I synthesized by the single pass I2 method. Appl. Radiat. Isot. 2005, 62, 447–450; https://doi.org/10.1016/j.apradiso.2004.07.003.Search in Google Scholar

28. Suzuki, K., Yoshida, Y. Production of [13N]NH3 with ultra-high specific activity. Appl. Radiat. Isot. 1999, 50, 497–503; https://doi.org/10.1016/s0969-8043(98)00095-5.Search in Google Scholar

29. Suzuki, K., Yoshida, Y., Shikano, N., Kubodera, Y. Development of an automated equipment for the quick production of 13N-labeled compounds with high specific activity using anhydrous [13N]NH3. Appl. Radiat. Isot. 1999, 50, 1033–1038; https://doi.org/10.1016/s0969-8043(98)00178-x.Search in Google Scholar

30. Zhang, M. R., Ogawa, M., Yoshida, Y., Suzuki, K. Selective synthesis of [2-11C]2-iodopropane and [1-11C]iodoethane using the loop method by reacting methylmagnesium bromide with [11C]carbon dioxide. Appl. Radiat. Isot. 2006, 64, 216–222; https://doi.org/10.1016/j.apradiso.2005.07.025.Search in Google Scholar PubMed

31. Kato, K., Zhang, M. R., Suzuki, K. Rapid C-carboxylation of nitro[11C] methane for the synthesis of ethyl nitro[2-11C]acetate. Mol. Biosyst. 2008, 4, 53–55; https://doi.org/10.1039/b712734k.Search in Google Scholar PubMed

32. Arai, T., Zhang, M. R., Ogawa, M., Fukumura, T., Kato, K., Suzuki, K. Efficient and reproducible synthesis of [1-11C]acetyl chloride using the loop method. Appl. Radiat. Isot. 2009, 67, 296–300; https://doi.org/10.1016/j.apradiso.2008.09.013.Search in Google Scholar PubMed

33. Fujinaga, M., Ogawa, M., Kumata, K., Shimoda, Y., Kawamura, K., Zhang, M. R. Development of efficient construction of [11C]carbamate moiety using [11C]COCl2. J. Label. Compd. Radiopharm. 2015, 58, S333.Search in Google Scholar

34. Hanyu, M., Takada, Y., Hashimoto, H., Kawamura, K., Zhang, M. R., Fukumura, T. Carbon-11 radiolabeling of an oligopeptide containing tryptophan hydrochloride via a Pictet-Spengler reaction using carbon-11 formaldehyde. J. Pept. Sci. 2013, 19, 663–668; https://doi.org/10.1002/psc.2546.Search in Google Scholar PubMed

35. Ishii, H., Yamasaki, T., Yui, J., Zhang, Y. D., Hanyu, M., Ogawa, M., Nengaki, N., Tsuji, A. B., Terashima, Y., Matsushima, K., Zhang, M. R. Radiosynthesis of [thiocarbonyl-11C]disulfiram and its first PET study in mice. Bioorg. Med. Chem. Lett. 2020, 30, 126998; https://doi.org/10.1016/j.bmcl.2020.126998.Search in Google Scholar PubMed

36. Obokata, N., Seki, C., Hirata, T., Maeda, J., Ishii, H., Nagai, Y., Matsumura, T., Takakuwa, M., Fukuda, H., Minamimoto, T., Kawamura, K., Zhang, M. R., Nakajima, T., Saijo, T., Higuchi, M. Synthesis and preclinical evaluation of [11C]MTP38 as a novel PET ligand for phosphodiesterase 7 in the brain. Eur. J. Nucl. Med. Mol. Imag. 2021, 48, 3101–3112; https://doi.org/10.1007/s00259-021-05269-4.Search in Google Scholar PubMed PubMed Central

37. Zhang, M-R., Kumata, K., Suzuki, K. A practical route for synthesizing a PET ligand containing [18F]fluorobenzene using reaction of diphenyliodonium salt with [18F]F–. Tetrahedron Lett. 2007, 48, 8632–8635; https://doi.org/10.1016/j.tetlet.2007.10.025.Search in Google Scholar

38. Zhang, M-R., Suzuki, K. [18F]Fluoroalkyl agents: synthesis, reactivity and application for development of PET ligands in molecular imaging. Curr. Top. Med. Chem. 2007, 7, 1817–1828; https://doi.org/10.2174/156802607782507448.Search in Google Scholar

39. Zhang, M-R., Ogawa, M., Furutsuka, K., Yoshida, Y., Suzuki, K. [18F]Fluoromethyl iodide ([18F]FCH2I): preparation and reactions with phenol, thiophenol, amide and amine functional groups. J. Fluor. Chem. 2004, 125, 1879–1886; https://doi.org/10.1016/j.jfluchem.2004.06.017.Search in Google Scholar

40. Zhang, M-R., Furutsuka, K., Yoshida, Y., Suzuki, K. How to increase the reactivity of [18F]fluoroethyl bromide: [18F]fluoroethylation of amine, phenol and amide functional groups with [18F]FEtBr, [18F]FEtBr/NaI and [18F]FEtOTf. J. Label. Compd. Radiopharm. 2003, 46, 587–598; https://doi.org/10.1002/jlcr.703.Search in Google Scholar

41. Zhang, M-R., Tsuchiyama, A., Haradahira, T., Yoshida, Y., Furutsuka, K., Suzuki, K. Development of an automated system for synthesizing 18F-labeled compounds using [18F]fluoroethyl bromide as a synthetic precursor. Appl. Radiat. Isot. 2002, 57, 335–342; https://doi.org/10.1016/s0969-8043(02)00075-1.Search in Google Scholar

42. Suzuki, K., Blessing, G., Qaim, S. M., Stoecklin, G. Production of high-purity Kr-77 via the 77Se (3He,3n)77Kr process. Int. J. Appl. Radiat. Isot. 1982, 33, 1445–1448; https://doi.org/10.1016/0020-708x(82)90184-3.Search in Google Scholar

43. Suzuki, K., Iwata, R. A multi-target assembly in an irradiation with high energy particles. Simultaneous production of 123I, 62Zn, 13N. Int. J. Appl. Radiat. Isot. 1977, 28, 663–665; https://doi.org/10.1016/0020-708x(77)90010-2.Search in Google Scholar

44. Nagatsu, K., Kubodera, A., Suzuki, K. Excitation function measurements of 40Ar(p,3n)38K, 40Ar(p,2pn)38Cl and 40Ar(p,2p)39Cl reactions. Appl. Radiat. Isot. 1999, 50, 389–396; https://doi.org/10.1016/s0969-8043(98)00096-7.Search in Google Scholar

45. Szélecsényi, F., Steyn, G. F., Kovács, Z., Vermeulen, C., Nagatsu, K., Zhang, M. R., Suzuki, K. Excitation functions of natZr + p nuclear processes up to 70 MeV: new measurements and compilation. Nucl. Instrum. Methods Phys. Res., Sect. B 2015, 343, 173–191.10.1016/j.nimb.2014.11.081Search in Google Scholar

46. Azony, K. E., Suzuki, K., Fukumura, T., Szélecsényi, F., Kovács, Z. Excitation functions of proton induced reactions on natural selenium up to 62 MeV. Radiochim. Acta 2009, 97, 71–77; https://doi.org/10.1524/ract.2009.1580.Search in Google Scholar

47. Azony, K. M. E., Suzuki, K., Fukumura, T., Szélecsényi, F., Kovács, Z. Proton induced reactions on natural tellurium up to 63 MeV: data validation and investigation of possibility of 124I production. Radiochim. Acta 2008, 96, 763–769; https://doi.org/10.1524/ract.2008.1530.Search in Google Scholar

48. Vermeulen, C., Steyn, G. F., Szélecsényi, F., Kovács, Z., Suzuki, K., Nagatsu, K., Fukumura, T., Hohn, A., Walt, T. N. Cross sections of proton-induced reactions on natGd with special emphasis on the production possibilities of 152Tb and 155Tb. Nucl. Instrum. Methods Phys. Res., Sect. B 2012, 275, 24–32; https://doi.org/10.1016/j.nimb.2011.12.064.Search in Google Scholar

49. Szélecsényi, F., Kovács, Z., Nagatsu, K., Zhang, M. R., Suzuki, K. Investigation of deuteron-induced reactions on natGd up to 30 MeV: possibility of production of medically relevant 155Tb and 161Tb radioisotopes. J. Radioanal. Nucl. Chem. 2016, 307, 1877–1881.10.1007/s10967-015-4528-0Search in Google Scholar

50. Khandaker, M. U., Nagatsu, K., Minegishi, K., Wakui, T., Zhang, M. R., Otuka, N. Study of deuteron-induced nuclear reactions on natural tungsten for the production of theranostic 186Re via AVF cyclotron up to 38 MeV. Nucl. Instrum. Methods Phys. Res., Sect. B 2017, 403, 51–68; https://doi.org/10.1016/j.nimb.2017.04.087.Search in Google Scholar

51. Obata, H., Khandaker, M. U., Furuta, E., Nagatsu, K., Zhang, M. R. Excitation functions of proton- and deuteron-induced nuclear reactions on natural iridium for the production of 191Pt. Appl. Radiat. Isot. 2018, 137, 250–260; https://doi.org/10.1016/j.apradiso.2018.03.021.Search in Google Scholar

52. Khandaker, M. U., Nagatsu, K., Obata, H., Minegishi, K., Zhang, M. R., Ali, S. K. I., Otuka, N. Excitation function of natCu(3He,x)65Zn nuclear reaction for 3He beam monitoring purpose. EPJ Web Conf. 2020, 239, 20009; https://doi.org/10.1051/epjconf/202023920009.Search in Google Scholar

53. Khandaker, M. U., Nagatsu, K., Obata, H., Minegishi, K., Zhang, M. R. Excitation functions of helion-induced nuclear reactions on natural titanium up to 55 MeV. Nucl. Instrum. Methods Phys. Res., Sect. B 2019, 445, 69–76; https://doi.org/10.1016/j.nimb.2019.03.011.Search in Google Scholar

54. Szélecsényi, F., Kovács, Z., Nagatsu, K., Zhang, M. R., Suzuki, K. Production cross sections of radioisotopes from 3He-particle induced nuclear reactions on natural titanium. Appl. Radiat. Isot. 2017, 119, 94–100.10.1016/j.apradiso.2016.10.016Search in Google Scholar

55. Szélecsényi, F., Kovács, Z., Nagatsu, K., Fukumura, T., Suzuki, K., Mukai, K. Investigation of direct production of 68Ga with low energy multiparticle accelerator. Radiochim. Acta 2012, 100, 5–11.10.1524/ract.2011.1896Search in Google Scholar

56. Szélecsényi, F., Suzuki, K., Kovács, Z., Takei, M., Okada, K. Alpha beam monitoring via natCu + alpha processes in the energy range from 40 to 60 MeV. Nucl. Instrum. Methods Phys. Res., Sect. B 2001, 184, 589–596.10.1016/S0168-583X(01)00793-5Search in Google Scholar

57. Szélecsényi, F., Suzuki, K., Kovács, Z., Takei, M., Okada, K. Production possibility of 60;61;62Cu radioisotopes by alpha induced reactions on cobalt for PET studies. Nucl. Instrum. Methods Phys. Res., Sect. B 2002, 187, 153–163.10.1016/S0168-583X(01)00923-5Search in Google Scholar

58. Nagatsu, K., Fukumura, T., Takei, M., Szélecsényi, F., Kovács, Z., Suzuki, K. Measurement of thick target yields of the natS(α,x)34mCl nuclear reaction and estimation of its excitation function up to 70 MeV. Nucl. Instrum. Methods Phys. Res., Sect. B 2008, 266, 709–713; https://doi.org/10.1016/j.nimb.2008.01.019.Search in Google Scholar

59. Nagatsu, K., Kubodera, A., Suzuki, K. A novel way of producing an aqueous solution of 38K+ via the 40Ar(p,3n)-process. Appl. Radiat. Isot. 1998, 49, 1505–1510; https://doi.org/10.1016/s0969-8043(98)00050-5.Search in Google Scholar

60. Tárkányi, F., Kovács, Z., Qaim, S. M., Stöcklin, G. Production of 38K via the 38Ar(p, n)-process at a small cyclotron. Int’l J Radiat Appl Instrum. Part A. Appl Radiat Isot. 1992, 43, 503–507.10.1016/0883-2889(92)90132-XSearch in Google Scholar

61. Takei, M., Nagatsu, K., Fukumura, T., Suzuki, K. Remote control production of an aqueous solution of no-carrier-added 34mCl– via the 32S(α,pn) nuclear reaction. Appl. Radiat. Isot. 2007, 65, 981–986; https://doi.org/10.1016/j.apradiso.2007.04.015.Search in Google Scholar

62. Qaim, S. M. Development of novel positron emitters for medical applications: nuclear and radiochemical aspects. Radiochim. Acta 2011, 99, 611–625; https://doi.org/10.1524/ract.2011.1870.Search in Google Scholar

63. Fujibayashi, Y., Matsumoto, K., Yonekura, Y., Konishi, J., Yokoyama, A. A new zinc-62/copper-62 generator as copper-62 source for PET radiopharmaceuticals. J. Nucl. Med. 1989, 30, 1838–1842.Search in Google Scholar

64. Fukumura, T., Okada, K., Suzuki, H., Nakao, R., Mukai, K., Szélecsényi, F., Kovács, Z., Suzuki, K. An improved 62Zn/62Cu generator based on a cation exchanger and its fully remote-controlled preparation for clinical use. Nucl. Med. Biol. 2006, 33, 821–827; https://doi.org/10.1016/j.nucmedbio.2006.05.003.Search in Google Scholar

65. Szélecsényi, F., Blessing, G., Qaim, S. M. Excitation functions of Proton induced nuclear reactions on enriched 61Ni and 64Ni; possibility of production of nocarrier-added 61Cu and 64Cu at a small cyclotron. Appl. Radiat. Isot. 1993, 44, 575–580.10.1016/0969-8043(93)90172-7Search in Google Scholar

66. Hao, G., Fukumura, T., Nakao, R., Suzuki, H., Szélecsényi, F., Kovács, Z., Suzuki, K. Cation exchange separation of 61Cu2+ from natCo targets and preparation of 61Cu-DOTA-HSA as a blood pool agent. Appl. Radiat. Isot. 2009, 67, 511; https://doi.org/10.1016/j.apradiso.2008.12.004.Search in Google Scholar

67. McCarthy, D. W., Shefer, R. E., Klinkowstein, R. E., Bass, L. A., Margeneau, W. H., Cutler, C. S., Anderson, C. J., Welch, M. J. Efficient production of high specific activity 64Cu using a biomedical cyclotron. Nucl. Med. Biol. 1997, 24, 35–43; https://doi.org/10.1016/s0969-8051(96)00157-6.Search in Google Scholar

68. Ohya, T., Nagatsu, K., Suzuki, H., Fukada, M., Minegishi, K., Hanyu, M., Fukumura, T., Zhang, M-R. Efficient preparation of high-quality 64Cu for routine use. Nucl. Med. Biol. 2016, 43, 685–691; https://doi.org/10.1016/j.nucmedbio.2016.07.007.Search in Google Scholar PubMed

69. Aung, W., Jin, Z-H., Furukawa, T., Claron, M., Boturyn, D., Sogawa, C., Tsuji, A. B., Wakizaka, H., Fukumura, T., Fujibayashi, Y., Dumy, P., Saga, T. Micro-positron emission tomography/contrast-enhanced computed tomography imaging of orthotopic pancreatic tumor-bearing mice using the αvβ3 integrin tracer 64Cu-labeled cyclam-RAFT-c(-RGDfK-)4. Mol. Imag. 2013, 12, 376–387; https://doi.org/10.2310/7290.2013.00054.Search in Google Scholar

70. Jin, Z-H., Furukawa, T., Sogawa, C., Claron, M., Aung, W., Tsuji, A. B., Wakizaka, H., Zhang, M-R., Boturyn, D., Dumy, P., Fujibayashi, Y., Saga, T. PET imaging and biodistribution analysis of the effects of succinylated gelatin combined with L-lysine on renal uptake and retention of 64Cu-cyclam-RAFT-c(-RGDfK-)4 in vivo. Eur. J. Pharm. Biopharm. 2014, 86, 478–486; https://doi.org/10.1016/j.ejpb.2013.11.006.Search in Google Scholar PubMed

71. Yoshii, Y., Matsumoto, H., Yoshimoto, M., Furukawa, T., Morokoshi, Y., Sogawa, C., Zhang, M-R., Wakizaka, H., Yoshii, H., Fujibayashi, Y., Saga, T. Controlled administration of penicillamine reduces radiation exposure in critical organs during 64Cu-ATSM internal radiotherapy: a novel strategy for liver protection. PLoS One 2014, 9, e86996; https://doi.org/10.1371/journal.pone.0086996.Search in Google Scholar PubMed PubMed Central

72. Matsumoto, H., Igarashi, C., Kaneko, E., Hashimoto, H., Suzuki, H., Kawamura, K., Zhang, M-R., Higashi, T., Yoshii, Y. Process development of [64Cu]Cu-ATSM: efficient stabilization and sterilization for therapeutic applications. J Radianal Nucl Chem 2019, 322, 467–475; https://doi.org/10.1007/s10967-019-06738-9.Search in Google Scholar

73. Fujiwara, K., Akiba, H., Tsuji, A. B., Sudo, H., Sugyo, A., Nagatsu, K., Zhang, M-R., Iwanari, H., Kusano-Arai, O., Kudo, S., Kikuchi, C., Tsumoto, K., Momose, T., Hamakubo, T., Higashi, T. 64Cu-labeled minibody D2101 visualizes CDH17-positive gastric cancer xenografts with short waiting time. Nucl. Med. Commun. 2020, 41, 688–695; https://doi.org/10.1097/MNM.0000000000001203.Search in Google Scholar PubMed

74. Hu, K., Xie, L., Zhang, Y., Hanyu, M., Yang, Z., Nagatsu, K., Suzuki, H., Ouyang, J., Ji, X., Wei, J., Xu, H., Farokhzad, O. C., Liang, S. H., Wang, L., Tao, W., Zhang, M.-R. Marriage of black phosphorus and Cu2+ as effective photothermal agents for PET-guided combination cancer therapy. Nat. Commun. 2020, 11, 2778; https://doi.org/10.1038/s41467-020-16513-0.Search in Google Scholar PubMed PubMed Central

75. Hu, K., Wu, W., Xie, L., Geng, H., Zhang, Y., Hanyu, M., Zhang, L., Liu, Y., Nagatsu, K., Suzuki, H., Guo, J., Wu, Y., Li, Z., Wang, F., Zhang, M.-R. Whole-body PET tracking of a D-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors. Acta Pharm. Sin. B 2022, 12, 1363–1376; https://doi.org/10.1016/j.apsb.2021.09.016.Search in Google Scholar PubMed PubMed Central

76. Stoll, T., Kastleiner, S., Shubin, Y. 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. Radiochim. Acta 2002, 90, 309–313; https://doi.org/10.1524/ract.2002.90.6.309.Search in Google Scholar

77. Ohya, T., Nagatsu, K., Suzuki, H., Fukada, M., Minegishi, K., Hanyu, M., Zhang, M-R. Small-scale production of 67Cu for a preclinical study via the 64Ni(α, p)67Cu channel. Nucl. Med. Biol. 2018, 59, 56–60; https://doi.org/10.1016/j.nucmedbio.2018.01.002.Search in Google Scholar PubMed

78. Jin, Z. H., Furukawa, T., Ohya, T., Degardin, M., Sugyo, A., Tsuji, A. B., Fujibayashi, Y., Zhang, M-R., Higashi, T., Boturyn, D., Dumy, P., Saga, T. 67Cu-radiolabeling of a multimeric RGD peptide for αVβ3 integrin-targeted radionuclide therapy: stability, therapeutic efficacy, and safety studies in mice. Nucl. Med. Commun. 2017, 38, 347–355; https://doi.org/10.1097/mnm.0000000000000646.Search in Google Scholar

79. Ohya, T., Nagatsu, K., Hanyu, M., Minegishi, K., Zhang, M-R. Simple separation of 67Cu from bulk zinc by coprecipitation using hydrogen sulfide gas and silver nitrate. Radiochim. Acta 2020, 108, 469–476; https://doi.org/10.1515/ract-2019-3168.Search in Google Scholar

80. Nagatsu, K., Fukada, M., Minegishi, K., Suzuki, H., Fukumura, T., Yamazaki, H., Suzuki, K. Fully automated production of iodine-124 using a vertical beam. Appl. Radiat. Isot. 2011, 69, 146–157; https://doi.org/10.1016/j.apradiso.2010.09.010.Search in Google Scholar

81. Nagatsu, K., Suzuki, H., Fukada, M., Minegishi, K., Tsuji, A. B., Fukumura, T. An alumina ceramic target vessel for the remote production of metallic radioinuclides by in situ target dissolution. Nucl. Med. Biol. 2012, 39, 1281–1285; https://doi.org/10.1016/j.nucmedbio.2012.05.010.Search in Google Scholar

82. Minegishi, K., Nagatsu, K., Fukada, M., Suzuki, H., Ohya, T., Zhang, M. R. Production of Sc-43 and Sc-47 from a powdery CaO target via the nat/44Ca(α, x)-channel. Appl. Radiat. Isot. 2016, 116, 8–12; https://doi.org/10.1016/j.apradiso.2016.07.017.Search in Google Scholar

83. Khandaker, M. U., Nagatsu, K., Minegishi, K., Zhang, M. R., Jalilian, A. R., Bradley, D. A. Cyclotron production of no carrier added 186gRe radionuclide for theranostic applications. Appl. Radiat. Isot. 2020, 166, 109428; https://doi.org/10.1016/j.apradiso.2020.109428.Search in Google Scholar

84. Scholten, B., Kovács, Z., Tárkányi, F., Qaim, S. M. Excitation functions of 124Te(p,xn)124,123I reactions from 6 to 31 MeV with special reference to the production of 124I at a small cyclotron. Appl. Radiat. Isot. 1995, 46, 255–259; https://doi.org/10.1016/0969-8043(94)00145-p.Search in Google Scholar

85. Steyn, G. F., Vermeulen, C., Szélecsényi, F., Kovács, Z., Suzuki, K., Fukumura, T. Excitation functions of proton induced reactions on 89Y and 93Nb with emphasison the production of selected radio-zirconiums. J. Kor. Phys. Soc. 2011, 59, 1991–1994; https://doi.org/10.3938/jkps.59.1991.Search in Google Scholar

86. Szkliniarz, K., Sitarz, M., Walczak, R., Jastrzębski, J., Bilewicz, A., Choiński, J., Jakubowski, A., Majkowska, A., Stolarz, A., Trzcińska, A., Zipper, W. Production of medical Sc radioisotopes with an alpha particle beam. Appl. Radiat. Isot. 2016, 118, 182–189; https://doi.org/10.1016/j.apradiso.2016.07.001.Search in Google Scholar PubMed

87. Carzaniga, T. S., Braccini, S. Cross-section measurement of 44mSc, 47Sc, 48Sc and 47Ca for an optimized 47Sc production with an 18 MeV medical PET cyclotron. Appl. Radiat. Isot. 2019, 143, 18–23; https://doi.org/10.1016/j.apradiso.2018.10.015.Search in Google Scholar PubMed

88. Khandaker, M. U., Nagatsu, K., Minegishi, K., Wakui, T., Zhang, M. R., Otuka, N. Study of deuteron-induced nuclear reactions on natural tungsten for the production of theranostic 186Re via AVF cyclotron up to 38 MeV. Nucl. Instrum. Methods Phys. Res., Sect. B 2017, 403, 51–68; https://doi.org/10.1016/j.nimb.2017.04.087.Search in Google Scholar

89. Kaminski, M. S., Zasadny, K. R., Francis, I. R., Milik, A. W., Ross, C. W., Moon, S. D., Crawford, S. M., Burgess, J. M., Petry, N. A., Butchko, G. M., Glenn, S. D., Wahl, R. L. Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N. Engl. J. Med. 1993, 329, 459–465; https://doi.org/10.1056/nejm199308123290703.Search in Google Scholar

90. Knox, S. J., Goris, M. L., Trisler, K., Negrin, R., Davis, T., Liles, T. M., Grillo-Lo’pez, A., Chinn, P., Varns, C., Ning, S. C., Fowler, S., Deb, N., Becker, M., Marquez, C., Levy, R. Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma. Clin. Cancer Res. 1996, 2, 457–470.10.1016/0360-3016(95)97811-ESearch in Google Scholar

91. Meredith, R. F., Knox, S. J. Clinical development of radioimmunotherapy for B-cell non-Hodgkin’s lymphoma. Int. J. Radiat. Oncol. Biol. Phys. 2006, 66, S15–S22; https://doi.org/10.1016/j.ijrobp.2006.04.059.Search in Google Scholar PubMed

92. Corson, D. R., MacKenzie, K. R., Segrè, E. Artificially radioactive element 85. Phys. Rev. 1940, 58, 672; https://doi.org/10.1103/physrev.58.672.Search in Google Scholar

93. Nagatsu, K., Minegishi, K., Fukada, M., Suzuki, H., Hasegawa, S., Zhang, M. R. Production of 211At by a vertical irradiation method. Appl. Radiat. Isot. 2014, 94, 363–371; https://doi.org/10.1016/j.apradiso.2014.09.012.Search in Google Scholar PubMed

94. Li, H., Morokoshi, Y., Nagatsu, K., Kamada, T., Hasegawa, S. Locoregional therapy with a-emitting trastuzumab peritoneal metastasis of human epidermal growth factor receptor 2-positive gastric cancer in mice. Cancer Sci. 2017, 108, 1648–1656; https://doi.org/10.1111/cas.13282.Search in Google Scholar PubMed PubMed Central

95. Ohsima, Y., Sudo, H., Watanabe, S., Nagatsu, K., Tsuji, A. B., Sakashita, T., Itoh, Y., Yoshinaga, K., Higashi, T., Ishioka, N. S. Antitumor effects of radionuclide treatment using α-emitting meta-211At-astatobenzylguanidine in a PC12 pheochromocytoma model. Eur. J. Nucl. Med. Mol. Imag. 2018, 45, 999–1010; https://doi.org/10.1007/s00259-017-3919-6.Search in Google Scholar PubMed PubMed Central

96. Xie, L., Hanyu, M., Fujinaga, M., Zhang, Y., Hu, K., Minegishi, K., Jiang, C., Kurosawa, F., Morokoshi, Y., Li, H. K., Hasegawa, S., Nagatsu, K., Zhang, M. R. 131I-IITM and 211At-AITM: two novel small-molecule radiopharmaceuticals targeting oncoprotein metabotropic glutamate receptor 1. J. Nucl. Med. 2020, 61, 242–248; https://doi.org/10.2967/jnumed.119.230946.Search in Google Scholar PubMed PubMed Central

97. Sudo, H., Tsuji, A. B., Sugyo, A., Nagatsu, K., Minegishi, K., Ishioka, N. S., Ito, H., Yoshinaga, K., Higashi, T. Preclinical evaluation of the acute radiotoxicity of the α-emitting molecular-targeted therapeutic agent 211At-MABG for the treatment of malignant pheochromocytoma in normal mice. Trans. Oncol. 2019, 12, 879–888; https://doi.org/10.1016/j.tranon.2019.04.008.Search in Google Scholar PubMed PubMed Central

98. Kodaira, S., Morokoshi, Y., Li, H. K., Konishi, T., Kurano, M., Hasegawa, S. Evidence of local concentration of α-particles from 211At-labeled antibodies in liver metastasis tissue. J. Nucl. Med. 2019, 60, 497–501; https://doi.org/10.2967/jnumed.118.216853.Search in Google Scholar PubMed PubMed Central

99. Shi, X., Li, Q., Zhang, L., Hanyu, M., Xie, L., Hu, K., Nagatsu, K., Zhang, C., Wu, Z., Wang, F., Zhang, M. R., Yang, K., Zhu, R. 211At-Labeled polymer nanoparticles for targeted radionuclide therapy of glucose-dependent insulinotropic polypeptide receptor (GIPR)-Overexpressed cancer. Bioconjugate Chem. 2021, 32, 1763–1772; https://doi.org/10.1021/acs.bioconjchem.1c00263.Search in Google Scholar PubMed

100. Cyclotrons used for radionuclide production. Accelerator knowledge portal. IAEA web site. https://nucleus.iaea.org/sites/accelerators/Pages/Cyclotron.aspx (accessed Jun 15, 2021).Search in Google Scholar

101. Supply platform of short-lived radioisotopes, managed by leading accelerator institutes in Japan (web site; Japanese). https://www.rcnp.osaka-u.ac.jp/∼ripf/index.html (accessed Jun 15, 2021).Search in Google Scholar

102. Kratochwil, C., Bruchertseifer, F., Giesel, F. L., Weis, M., Verburg, F. A., Mottaghy, F., Kopka, K., Apostolidis, C., Haberkorn, U., Morgenstern, A. 225Ac-PSMA-617 for PSMA-targeted α-radiation therapy of metastatic castration-resistant prostate cancer. J. Nucl. Med. 2016, 57, 1941–1944; https://doi.org/10.2967/jnumed.116.178673.Search in Google Scholar PubMed

103. National Isotope Development Center. Product Catalog, Ac-225 (Accelerator-produced), web site. https://www.isotopes.gov/sites/default/files/2021-02/Ac-225%20Accel%20Produced_1.pdf (accessed Oct 30, 2021).Search in Google Scholar

104. Robertson, A. K. H., McNeil, B. L., Yang, H., Gendron, D., Perron, R., Radchenko, V., Zeisler, S., Causey, P., Schaffer, P. 232Th-Spallation-Produced 225Ac with reduced 227Ac content. Inorg. Chem. 2020, 59, 12156–12165; https://doi.org/10.1021/acs.inorgchem.0c01081.Search in Google Scholar PubMed

105. Nagatsu, K., Suzuki, H., Fukada, M., Ito, T., Ichinose, J., Honda, Y., Minegishi, K., Higashi, T., Zhang, M. R. Cyclotron production of 225Ac from an electroplated 226Ra target. Eur. J. Nucl. Med. Mol. Imag. 2021, 49, 279–289; https://doi.org/10.1007/s00259-021-05460-7.Search in Google Scholar PubMed PubMed Central

106. Apostolidis, C., Molinet, R., McGinley, J., Abbas, K., Möllenbeck, J., Morgenstern, A. Cyclotron production of Ac-225 for targeted alpha therapy. Appl. Radiat. Isot. 2005, 62, 383–387; https://doi.org/10.1016/j.apradiso.2004.06.013.Search in Google Scholar PubMed

107. Qaim, S. M., Spahn, I., Scholten, B., Neumaier, B. Uses of alpha particles, especially in nuclear reaction studies and medical radionuclide production. Radiochim. Acta 2016, 104, 601–624; https://doi.org/10.1515/ract-2015-2566.Search in Google Scholar

108. Uddin, M. S., Scholten, B., Hermanne, A., Sudár, S., Coenen, H. H., Qaim, S. M. Radiochemical determination of cross sections of alpha particle induced reactions on 192Os for the production of the therapeutic radionuclide 193mPt. Appl. Radiat. Isot. 2010, 68, 2001–2006; https://doi.org/10.1016/j.apradiso.2010.05.002.Search in Google Scholar PubMed

109. Uddin, M. S., Hermanne, A., Scholten, B., Spellerberg, S., Coenen, H. H., Qaim, S. M. Small scale production of high purity 193mPt by the 192Os(α,3n)-process. Radiochim. Acta 2011, 99, 131–135; https://doi.org/10.1524/ract.2011.1807.Search in Google Scholar

110. Obata, H., Minegishi, K., Nagatsu, K., Zhang, M. R., Shinohara, A. Production of 191Pt from an iridium target by vertical beam irradiation and simultaneous alkali fusion. Appl. Radiat. Isot. 2019, 149, 31–37; https://doi.org/10.1016/j.apradiso.2019.04.007.Search in Google Scholar PubMed

111. Obata, H., Minegishi, K., Nagatsu, K., Ogawa, M., Zhang, M. R. Synthesis of no-carrier-added [188, 189, 191Pt]cisplatin from a cyclotron produced 188, 189, 191PtCl42− complex. Sci. Rep. 2021, 11, 8140; https://doi.org/10.1038/s41598-021-87576-2.Search in Google Scholar PubMed PubMed Central

112. Obata, H., Tsuji, A. B., Sudo, H., Sugyo, A., Minegishi, K., Nagatsu, K., Ogawa, M., Zhang, M. R. In vitro evaluation of No-carrier-added radiolabeled cisplatin ([189, 191Pt]cisplatin) emitting auger electrons. Int. J. Mol. Sci. 2021, 22, 4622; https://doi.org/10.3390/ijms22094622.Search in Google Scholar PubMed PubMed Central

Received: 2021-11-15
Accepted: 2022-02-25
Published Online: 2022-04-21
Published in Print: 2022-06-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial: Diamond Jubilee Issue
  3. Sixty years of Radiochimica Acta: a brief overview with emphasis on the last 10 years
  4. A. Chemistry of Radioelements
  5. Five decades of GSI superheavy element discoveries and chemical investigation
  6. Chemistry of the elements at the end of the actinide series using their low-energy ion-beams
  7. Sonochemistry of actinides: from ions to nanoparticles and beyond
  8. Theoretical insights into the reduction mechanism of neptunyl nitrate by hydrazine derivatives
  9. The speciation of protactinium since its discovery: a nightmare or a path of resilience
  10. On the volatility of protactinium in chlorinating and brominating gas media
  11. The aqueous chemistry of radium
  12. B. Energy Related Radiochemistry
  13. Selective actinide(III) separation using 2,6-bis[1-(propan-1-ol)-1,2,3-triazol-4-yl]pyridine (PyTri-Diol) in the innovative-SANEX process: laboratory scale counter current centrifugal contactor demonstration
  14. Fate of Neptunium in nuclear fuel cycle streams: state-of-the art on separation strategies
  15. Uranium adsorption – a review of progress from qualitative understanding to advanced model development
  16. Targeted synthesis of carbon-supported titanate nanofibers as host structure for nuclear waste immobilization
  17. Progress of energy-related radiochemistry and radionuclide production in the Republic of Korea
  18. C. Nuclear Data
  19. How accurate are half-life data of long-lived radionuclides?
  20. Status of the decay data for medical radionuclides: existing and potential diagnostic γ emitters, diagnostic β+ emitters and therapeutic radioisotopes
  21. An overview of nuclear data standardisation work for accelerator-based production of medical radionuclides in Pakistan
  22. An overview of activation cross-section measurements of some neutron and charged-particle induced reactions in Bangladesh
  23. Nuclear reaction data for medical and industrial applications: recent contributions by Egyptian cyclotron group
  24. Nuclear data for light charged particle induced production of emerging medical radionuclides
  25. D. Radionuclides and Radiopharmaceuticals
  26. The role of chemistry in accelerator-based production and separation of radionuclides as basis for radiolabelled compounds for medical applications
  27. Production of neutron deficient rare earth radionuclides by heavy ion activation
  28. Evaluation of 186WS2 target material for production of high specific activity 186Re via proton irradiation: separation, radiolabeling and recovery/recycling
  29. Special radionuclide production activities – recent developments at QST and throughout Japan
  30. China’s radiopharmaceuticals on expressway: 2014–2021
  31. E. Environmental Radioactivity
  32. A summary of environmental radioactivity research studies by members of the Japan Society of Nuclear and Radiochemical Sciences
https://doi.org/10.1515/ract-2021-1124
Keywords for this article
cyclotron; NIRS; QST; radioisotope production; radiopharmaceuticals

Articles in the same Issue

  1. Frontmatter
  2. Editorial: Diamond Jubilee Issue
  3. Sixty years of Radiochimica Acta: a brief overview with emphasis on the last 10 years
  4. A. Chemistry of Radioelements
  5. Five decades of GSI superheavy element discoveries and chemical investigation
  6. Chemistry of the elements at the end of the actinide series using their low-energy ion-beams
  7. Sonochemistry of actinides: from ions to nanoparticles and beyond
  8. Theoretical insights into the reduction mechanism of neptunyl nitrate by hydrazine derivatives
  9. The speciation of protactinium since its discovery: a nightmare or a path of resilience
  10. On the volatility of protactinium in chlorinating and brominating gas media
  11. The aqueous chemistry of radium
  12. B. Energy Related Radiochemistry
  13. Selective actinide(III) separation using 2,6-bis[1-(propan-1-ol)-1,2,3-triazol-4-yl]pyridine (PyTri-Diol) in the innovative-SANEX process: laboratory scale counter current centrifugal contactor demonstration
  14. Fate of Neptunium in nuclear fuel cycle streams: state-of-the art on separation strategies
  15. Uranium adsorption – a review of progress from qualitative understanding to advanced model development
  16. Targeted synthesis of carbon-supported titanate nanofibers as host structure for nuclear waste immobilization
  17. Progress of energy-related radiochemistry and radionuclide production in the Republic of Korea
  18. C. Nuclear Data
  19. How accurate are half-life data of long-lived radionuclides?
  20. Status of the decay data for medical radionuclides: existing and potential diagnostic γ emitters, diagnostic β+ emitters and therapeutic radioisotopes
  21. An overview of nuclear data standardisation work for accelerator-based production of medical radionuclides in Pakistan
  22. An overview of activation cross-section measurements of some neutron and charged-particle induced reactions in Bangladesh
  23. Nuclear reaction data for medical and industrial applications: recent contributions by Egyptian cyclotron group
  24. Nuclear data for light charged particle induced production of emerging medical radionuclides
  25. D. Radionuclides and Radiopharmaceuticals
  26. The role of chemistry in accelerator-based production and separation of radionuclides as basis for radiolabelled compounds for medical applications
  27. Production of neutron deficient rare earth radionuclides by heavy ion activation
  28. Evaluation of 186WS2 target material for production of high specific activity 186Re via proton irradiation: separation, radiolabeling and recovery/recycling
  29. Special radionuclide production activities – recent developments at QST and throughout Japan
  30. China’s radiopharmaceuticals on expressway: 2014–2021
  31. E. Environmental Radioactivity
  32. A summary of environmental radioactivity research studies by members of the Japan Society of Nuclear and Radiochemical Sciences
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