Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Radiochimica Acta

International Journal for chemical aspects of nuclear science and technology

Editor-in-Chief: Qaim, Syed M.

IMPACT FACTOR 2018: 1.339

CiteScore 2018: 1.20

SCImago Journal Rank (SJR) 2018: 0.333
Source Normalized Impact per Paper (SNIP) 2018: 0.720

See all formats and pricing
More options …
Ahead of print


Simple separation of 67Cu from bulk zinc by coprecipitation using hydrogen sulfide gas and silver nitrate

Tomoyuki Ohya
  • Corresponding author
  • Department of Radiopharmaceuticals Development, National Institutes for Quantum and Radiological Science and Technology (NIRS-QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Kotaro Nagatsu
  • National Institutes for Quantum and Radiological Science and Technology (NIRS-QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Masayuki Hanyu
  • National Institutes for Quantum and Radiological Science and Technology (NIRS-QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Katsuyuki Minegishi
  • National Institutes for Quantum and Radiological Science and Technology (NIRS-QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ming-Rong Zhang
  • National Institutes for Quantum and Radiological Science and Technology (NIRS-QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2019-10-17 | DOI: https://doi.org/10.1515/ract-2019-3168


Copper-67 (67Cu), a feasible radionuclide for diagnosis and radiotherapy, is commercially generated from a bulk zinc (Zn) target using the 68Zn(p, 2p)67Cu and 68Zn(γ, p)67Cu nuclear reactions. Because it uses a large amount of zinc, the separation is complex – requiring a combination of three ion exchange columns – and is time-consuming (about 1 day). We developed a quick and easy separation method referred to as “double coprecipitation” using H2S gas and silver nitrate as coprecipitation agents in place of ion exchange columns. We compared this method with a conventional separation method using three ion exchange columns (AG50W-X8, AG1-X8, and Chelex-100) for a natural zinc (natZn) target irradiated by a proton beam. The product quality and the recovery rate with the new method were competitive with the conventional method, and the total operation time was reduced from 1 day to <3 h.

Keywords: 67Cu; bulk zinc; coprecipitation; separation; silver precipitate


  • 1.

    Blower, P. J., Lewis, J. S., Zweit, J.: Copper radionuclides and radiopharmaceuticals in nuclear medicine. Nucl. Med. Biol. 23, 957 (1996).CrossrefPubMedGoogle Scholar

  • 2.

    Novak-Hofer, I., Schubiger, P. A.: Copper-67 as a therapeutic nuclide for radioimmunotherapy. Eur. J. Nucl. Med. 29, 821 (2002).CrossrefGoogle Scholar

  • 3.

    Smith, N. A., Bowers, D. L., Ehst, D. A.: The production, separation, and use of 67Cu for radioimmunotherapy: a review. Appl. Radiat. Isot. 70, 2377 (2012).CrossrefPubMedGoogle Scholar

  • 4.

    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. Comm. 38, 347 (2017).CrossrefGoogle Scholar

  • 5.

    Qaim, S. M., Scholten, B., Neumaier, B.: New developments in the production of theranostic pairs of radionuclides. J. Radioanal. Nucl. Chem. 318, 1493 (2018).CrossrefGoogle Scholar

  • 6.

    National Nuclear Data Center: NuDat 2.7., Brookhaven National Laboratory, NY. Accessed March 12, 2019. http://www.nndc.bnl.gov/chart/.

  • 7.

    Mirzadeh, S., Mausner, L. F., Srivastava, S. C.: Production of no-carrier added 67Cu. Appl. Radiat. Isot. 37, 29 (1986).CrossrefGoogle Scholar

  • 8.

    Dasgupta, A. K., Mausner, L. F., Srivastava, S. C.: A new separation procedure for 67Cu from proton irradiated Zn. Appl. Radiat. Isot. 42, 371 (1991).CrossrefGoogle Scholar

  • 9.

    Schwarzbach, R., Zimmermann, K., Bläuenstein, P., Smith, A., Schubiger, P. A.: Development of a simple and selective separation of 67Cu from irradiated zinc for use in antibody labelling: a comparison of methods. Appl. Radiat. Isot. 46, 329 (1995).PubMedCrossrefGoogle Scholar

  • 10.

    Shikata, E.: Research of radioisotope production with fast neutrons, (VI) preparation of Cu-67. J. Nucl. Sci. Technol. 1, 171 (1964).Google Scholar

  • 11.

    Uddin, S., Uz-Zaman, R., Hossain, S. M., Qaim, S. M.: Radiochemical measurement of neutron-spectrum averaged cross sections for the formation of 64Cu and 67Cu via the (n,p) reaction at a TRIGA Mark-II reactor: feasibility of simultaneous production of the theragnostic pair 64Cu/67Cu. Radiochim. Acta 102, 473 (2014).Google Scholar

  • 12.

    Johnsen, A. M., Heidrich, B. J., Durrant, C. B., Bascom, A. J., Ünlü, K.: Reactor production of 64Cu and 67Cu using enriched zinc target material. J. Radioanal. Nucl. Chem. 305, 61 (2015).CrossrefGoogle Scholar

  • 13.

    Mausner, L. F., Kolsky, K. L., Joshi, V., Srivastava, S. C.: Radionuclide development at BNL for nuclear medicine therapy. Appl. Radiat. Isot. 49, 285 (1998).CrossrefPubMedGoogle Scholar

  • 14.

    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 90, 309 (2002).Google Scholar

  • 15.

    Medvedev, D. G., Mausner, L. F., Meinken, G. E., Kurczak, S. O., Schnakenberg, H., Dodge, C. J., Korach, E. M., Srivastava, S. C.: Development of a large scale production of 67Cu from 68Zn at the high energy proton accelerator: Closing the 68Zn cycle. Appl. Radiat. Isot. 70, 423 (2012).CrossrefPubMedGoogle Scholar

  • 16.

    Kastleiner, S., Coenen, H. H., Qaim, S. M.: Possibility of production of 67Cu at a small-sized cyclotron via the (p,α)-reaction on enriched 70Zn. Radiochim. Acta 84, 107 (1999).Google Scholar

  • 17.

    Hilgers, K., Stoll, T., Skakun, Y., Coenen, H. H., Qaim, S. M.: Cross section measurements of the nuclear reactions natZn(d,x)64Cu, 66Zn(d,α)64Cu and 68Zn(p, αn)64Cu for production of 64Cu and technical developments for small-scale production of 67Cu via the 70Zn(p,α)67Cu process. Appl. Radiat. Isot. 59, 343 (2003).CrossrefPubMedGoogle Scholar

  • 18.

    Kozempel, J., Abbas, K., Simonelli, F., Bulgheroni, A., Holzwarth, U., Gibson, N.: Preparation of 67Cu via deuteron irradiation of 70Zn. Radiochim. Acta 100, 419 (2012).CrossrefGoogle Scholar

  • 19.

    Fujiki, K., Yano, S., Ito, T., Kumagai, Y., Murakami, Y., Kamigaito, O., Haba, H., Tanaka, K. A.: One-pot three-component double-click method for synthesis of [67Cu]-labeled biomolecular radiotherapeutics. Sci. Rep. 7, 1912 (2017).PubMedCrossrefGoogle Scholar

  • 20.

    Hosseini, S. F., Aboudzadeh, M., Sadeghi, M., Teymourlouy, A. A., Rostampour, M.: Assessment and estimation of 67Cu production yield via deuteron induced reactions on natZn and 70Zn. Appl. Radiat. Isot. 127, 137 (2017).PubMedCrossrefGoogle Scholar

  • 21.

    Ayzatskiy, N. I., Dikiy, N. P., Dovbnya, A. N., Lyashko, Y. V., Nikiforov, V. I., Shramenko, B. I., Tenishev, A. E., Torgovkin, A.V., Uvarov, V. L.: Comparison of Cu-67 production at cyclotron and electron accelerator. 18th international conference on cyclotrons and their applications (Cyclotrons 2007), INFN, Giardini-Naxos, Oct. (2007).Google Scholar

  • 22.

    Starovoitova, V. N., Tchelidze, L., Wells, D. P.: Production of medical radioisotopes with linear accelerators. Appl. Radiat. Isot. 85, 39 (2014).PubMedCrossrefGoogle Scholar

  • 23.

    Howard, S., Starovoitova, V. N.: Target optimization for the photonuclear production of radioisotopes. Appl. Radiat. Isot. 96, 162 (2015).PubMedWeb of ScienceCrossrefGoogle Scholar

  • 24.

    Spahn, I., Coenen, H. H., Qaim, S. M.: Enhanced production possibility of the therapeutic radionuclides 64Cu, 67Cu and 89Sr via (n,p) reactions induced by fast spectral neutrons. Radiochim. Acta 92, 183 (2004).Google Scholar

  • 25.

    Al-Abyad, M., Spahn, I., Sudar, S., Morsy, M., Comsan, M. N. H., Csikai, J., Qaim, S. M., Coenen, H. H.: Nuclear data for production of the therapeutic radionuclides 32P, 64Cu, 67Cu, 89Sr, 90Y and 153Sm via the (n,p) reaction: Evaluation of excitation function and its validation via integral cross-section measurement using a 14 MeV d(Be) neutron source. Appl. Radiat. Isot. 64, 717 (2006).CrossrefGoogle Scholar

  • 26.

    Kin, T., Nagai, Y., Iwamoto, N., Minato, F., Iwamoto, O., Hatsukawa, Y., Segawa, M., Harada, H., Konno, C., Ochiai, K., Takakura, K.: New production routes for medical isotopes 64Cu and 67Cu using accelerator neutrons. J. Phys. Soc. Jpn. 82, 034201 (2013).CrossrefGoogle Scholar

  • 27.

    Sato, N., Tsukada, K., Watanabe, S., Ishioka, N. S., Kawabata, M., Saeki, H., Nagai, Y., Kin, T., Minato, F., Iwamoto, N., Iwamoto, O.: First measurement of the radionuclide purity of the therapeutic isotope 67Cu produced by 68Zn(n,x) reaction using natC(d,n) neutrons. J. Phys. Soc. Jpn. 83, 073201 (2014).CrossrefGoogle Scholar

  • 28.

    Kawabata, M., Hashimoto, K., Saeki, H., Sato, N., Motoishi, S., Takakura, K., Konno, C., Nagai, Y.: Production and separation of 64Cu and 67Cu using 14 MeV neutrons. J. Radioanal. Nucl. Chem. 303, 1205 (2015).CrossrefGoogle Scholar

  • 29.

    Tanaka, S.: Reactions of nickel with alpha-particles. J. Phys. Soc. Jpn. 15, 2159 (1960).CrossrefGoogle Scholar

  • 30.

    Skakun, Y., Qaim, S. M.: Excitation function of the 64Ni(α,p)67Cu reaction for production of 67Cu. Appl. Radiat. Isot. 60, 33 (2004).CrossrefGoogle Scholar

  • 31.

    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. 59, 56 (2018).CrossrefPubMedGoogle Scholar

  • 32.

    Uddin, S., Kim, K., Nadeem, M., Sudár, S., Kim, G.: Measurements of excitation functions of α-particle induced reactions on natNi: possibility of production of the medical isotopes 61Cu and 67Cu. Radiochim. Acta 106, 87 (2018).CrossrefGoogle Scholar

  • 33.

    Gopalakrishna, A., Suryanarayana, S. V., Naik, H., Dixit, T. S., Nayak, B. K., Kumar, A., Maletha, P., Thakur, K., Deshpande, A., Krishnan, R., Kamaldeep, Banerjee, S., Saxena, A.: Production, separation and supply prospects of 67Cu with the development of fast neutron sources and photonuclear technology. Radiochim. Acta 106, 549 (2018).CrossrefGoogle Scholar

  • 34.

    Katabuchi, T., Watanabe, S., Ishioka, N. S., Iida, Y., Hanaoka, H., Endo, K., Matsuhashi, S.: Production of 67Cu via the 68Zn(p,2p)67Cu reaction and recovery of 68Zn target. J. Radioanal. Nucl. Chem. 277, 467 (2008).CrossrefGoogle Scholar

  • 35.

    Qaim, S. M., Sphan, I.: Development of novel radionuclide for medical applications. J. Label. Compd. Radiopharm. 61, 126 (2018).CrossrefGoogle Scholar

  • 36.

    Maiti, M., Lahiri, S., Kumar, D., Choudhury, D.: Separation of no-carrier-added astatine radionuclides from α-particle irradiated lead bismuth eutectic target: a classical method. Appl. Radiat. Isot. 127, 227 (2017).CrossrefWeb of ScienceGoogle Scholar

  • 37.

    Maiti, M., Lahiri, S., Tomar, B. S.: Separation of no-carrier-added 107,109Cd from proton induced silver target: classical chemistry still relevant. J. Radioanal. Nucl. Chem. 288, 115 (2011).CrossrefGoogle Scholar

  • 38.

    Dutta, B., Lahiri, S., Tomar, B. S.: Separation of no-carrier-added rhenium from bulk tantalum by precipitation technique. Sep. Sci. Technol. 48, 2468 (2013).CrossrefWeb of ScienceGoogle Scholar

  • 39.

    Minegishi, K., Nagatsu, K., Fukada, M., Suzuki, H., Ohya, T., Zhang, M.-R.: Production of scandium-43 and -47 from a powdery calcium oxide target via the Ca-nat/44(alpha,x)-channel. Appl. Radiat. Isot. 116, 8 (2016).CrossrefWeb of ScienceGoogle Scholar

  • 40.

    O’Brien Jr., H. A., Barnes, J. W., Taylor, W. A., Thomas, K. E., Bentley, G. E.: Method of producing 67Cu. United States Patent, Patent Number: 4,487,738, Date of Patent: Dec. 11, 1984.Google Scholar

  • 41.

    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. 69, 146 (2011).CrossrefPubMedWeb of ScienceGoogle Scholar

  • 42.

    SRIM-2013. The stopping and range of ions in matter. Download available from a web at http://www.srim.org/.

  • 43.

    Van So, L., Pellegrini, P., Katsifis, A., Howse, J., Greguric, I.: Radiochemical separation and quality assessment for the 68Zn target based 64Cu radioisotope production. J. Radioanal. Nucl. Chem. 277, 451 (2008).CrossrefGoogle Scholar

  • 44.

    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. 43, 685 (2016).CrossrefPubMedGoogle Scholar

  • 45.

    Qaim, S. M., Tárkányi, F., Capote, R. (Editors): Nuclear data for the production of therapeutic radionuclides, Technical Reports Series No. 473, IAEA, Vienna (2011), p. 1.Google Scholar

  • 46.

    Van Elteren, J. T., Kroon, K. J., Woroniecka, U. D., De Goeij, J. J. M.: Voltammetry detection of copper in high specific activity 64Cu. Appl. Radiat. Isot. 51, 15 (1999).CrossrefGoogle Scholar

  • 47.

    Sugo, Y., Hashimoto, K., Kawabata, M., Saeki, H., Sato, S., Tsukada, K., Nagai, Y.: Application of 67Cu produced by 68Zn(n, ń p+d)67Cu to biodistribution study in tumor-bearing mice. J. Phys. Soc. Jpn. 86, 023201 (2017).CrossrefGoogle Scholar

  • 48.

    Q3D elemental impurities guidance for industry: U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), MD (2015), p. 72.Google Scholar

  • 49.

    Nuclear Data Center: Table of isotope production cross sections (ACSELAM Library), Japan Atomic Energy Agency, Ibaraki. Accessed March 5, 2019 http://wwwndc.jaea.go.jp/ftpnd/sae/acl.html.

  • 50.

    Qaim, S. M.: The present and future of medical radionuclide production. Radiochim. Acta 100, 635 (2012).Web of ScienceCrossrefGoogle Scholar

About the article

Corresponding author: Tomoyuki Ohya, PhD, Department of Radiopharmaceuticals Development, National Institutes for Quantum and Radiological Science and Technology (NIRS-QST), 4-9-1 Anagawa, Inage-ku, Chiba263-8555, Japan

Received: 2019-05-08

Accepted: 2019-09-20

Published Online: 2019-10-17

Citation Information: Radiochimica Acta, 20193168, ISSN (Online) 2193-3405, ISSN (Print) 0033-8230, DOI: https://doi.org/10.1515/ract-2019-3168.

Export Citation

©2019 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in