Skip to main content
Log in

Photonuclear production of medical radiometals: a review of experimental studies

  • Published:
Journal of Radioanalytical and Nuclear Chemistry Aims and scope Submit manuscript

Abstract

Generally, short-lived medical isotopes and/or their generators are produced in nuclear reactors and cyclotrons. During the last decade, the rapidly increasing number of the studies on the photonuclear method of production of these isotopes has been observed. Experimental data on the production of ten radiometals (99Mo/99mTc, 47Sc, 67Cu, 225Ac, 177Lu, 44Ti/44Sc, 111In, 105Rh, 68Ge/68Ga, 188Re) in electron accelerators is presented in this review. The advantages of the photonuclear method for several isotopes were demonstrated, its future was discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Blower PJ (2015) A nuclear chocolate box: the periodic table of nuclear medicine. Dalt Trans 44:4819–4844. https://doi.org/10.1039/c4dt02846e

    Article  CAS  Google Scholar 

  2. Chakravarty R, Dash A (2012) Availability of yttrium-90 from strontium-90: a nuclear medicine perspective. Cancer Biother Radiopharm 27:621–641. https://doi.org/10.1089/cbr.2012.1285

    Article  CAS  PubMed  Google Scholar 

  3. Qaim SM (2020) Medical Radionuclide Production. De Gruyter, Berlin/Boston

    Google Scholar 

  4. Hashimoto K, Nagai Y (2014) Radionuclide production. Compr Biomed Phys 8:219–227. https://doi.org/10.1016/B978-0-444-53632-7.00614-6

    Article  Google Scholar 

  5. IAEA (2019) IAEA Annual Report

  6. Qaim SM (2011) Cyclotron production of medical radionuclides. In: Vértes A, Nagy S, Klencsár Z, Lovas RG, Rösch F (eds) Handbook of nuclear chemistry. Springer, Boston

    Google Scholar 

  7. Degering D, Unterricker S, Stolz W (1988) Excitation function of the 89Y(d,2n)89Zr reaction. J Radioanal Nucl Chem Lett 127:7–11. https://doi.org/10.1007/BF02165500

    Article  CAS  Google Scholar 

  8. Hermanne A, Takacs S, Goldberg MB et al (2006) Deuteron-induced reactions on Yb: measured cross sections and rationale for production pathways of carrier-free, medically relevant radionuclides. Nucl Instruments Methods Phys Res Sect B 247:223–231. https://doi.org/10.1016/j.nimb.2006.03.008

    Article  CAS  Google Scholar 

  9. Pramudita A (2011) Linacs for medical isotope production. Atom Indones 37:1. https://doi.org/10.17146/aij.2011.68

    Article  Google Scholar 

  10. Radioisotopes in Medicine. https://www.world-nuclear.org/information-library/non-power-nuclear-applications/radioisotopes-research/radioisotopes-in-medicine.aspx

  11. Dash A, Knapp FF, (Russ), Pillai MRA, (2013) 99Mo/99mTc separation: an assessment of technology options. Nucl Med Biol 40:167–176. https://doi.org/10.1016/j.nucmedbio.2012.10.005

    Article  CAS  PubMed  Google Scholar 

  12. Jang J, Uesaka M (2019) Influence of enriched 100Mo on Mo reaction yields. J Phys Commun. https://doi.org/10.1088/2399-6528/ab1d6b

    Article  Google Scholar 

  13. Qaim SM, Sudár S, Scholten B et al (2014) Evaluation of excitation functions of 100Mo(p, d+pn)99Mo and 100Mo(p,2n)99mTc reactions: Estimation of long-lived Tc-impurity and its implication on the specific activity of cyclotron-produced 99mTc. Appl Radiat Isot 85:101–113. https://doi.org/10.1016/j.apradiso.2013.10.004

    Article  CAS  PubMed  Google Scholar 

  14. Davydov MG, Mareskin SA (1993) About a possibility of preparation of 99Mo and 99mTc at electron accelerators. Radiokhimia (in Russian) 35:91–96

    CAS  Google Scholar 

  15. Uvarov VL, Dikiy NP, Dovbnya AN et al (1998) Electron accelerator’s production of Technetium-99m for nuclear medicine. Proc IEEE Part Accel Conf 3:3840–3841. https://doi.org/10.1109/pac.1997.753433

    Article  CAS  Google Scholar 

  16. Sabel’nikov A V., Maslov OD, Molokanova LG, et al (2006) Preparation of 99Mo and 99mTc by 100Mo(γ, n) photonuclear reaction on an electron accelerator, MT-25 microtron. Radiochemistry 48:191–194. https://doi.org/10.1134/S1066362206020172

    Article  CAS  Google Scholar 

  17. Ross C, Galea R, Saull P, Davidson W, Brown P, Brown D, Harvey J, Messina GWR, de JM, (2010) Using the 100Mo photo-neutron reaction to meet Canada’s requirement for 99mTc. Phys Can 66:19–24

    Google Scholar 

  18. Galea R, Wells RG, Ross CK et al (2013) A comparison of rat SPECT images obtained using 99mTc derived from 99Mo produced by an electron accelerator with that from a reactor. Phys Med Biol 58:2737–2750. https://doi.org/10.1088/0031-9155/58/9/2737

    Article  CAS  PubMed  Google Scholar 

  19. Naik H, Suryanarayana SV, Jagadeesan KC et al (2013) An alternative route for the preparation of the medical isotope 99Mo from the 238U(γ, f) and 100Mo(γ, n) reactions. J Radioanal Nucl Chem 295:807–816. https://doi.org/10.1007/s10967-012-1958-9

    Article  CAS  Google Scholar 

  20. Avagyan R, Avetisyan A, Kerobyan I, Dallakyan R (2014) Photo-production of 99Mo/99mTc with electron linear accelerator beam. Nucl Med Biol 41:705–709. https://doi.org/10.1016/j.nucmedbio.2014.04.132

    Article  CAS  PubMed  Google Scholar 

  21. Mang’era K, Ogbomo K, Zriba R, et al (2015) Processing and evaluation of linear accelerator-produced 99Mo/99mTc in Canada. J Radioanal Nucl Chem 305:79–85. https://doi.org/10.1007/s10967-015-3997-5

    Article  CAS  Google Scholar 

  22. Gopalakrishna A, Naik H, Suryanarayana SV et al (2016) Preparation of 99Mo from the 100Mo(γ, n) reaction and chemical separation of 99mTc. J Radioanal Nucl Chem 308:431–438. https://doi.org/10.1007/s10967-015-4481-y

    Article  CAS  Google Scholar 

  23. Sekimoto S, Tatenuma K, Suzuki Y et al (2017) Separation and purification of 99mTc from 99Mo produced by electron linear accelerator. J Radioanal Nucl Chem 311:1361–1366. https://doi.org/10.1007/s10967-016-4959-2

    Article  CAS  Google Scholar 

  24. Takeda T, Fujiwara M, Kurosawa M et al (2018) 99mTc production via the (γ, n) reaction on natural Mo. J Radioanal Nucl Chem 318:811–821. https://doi.org/10.1007/s10967-018-6078-8

    Article  CAS  Google Scholar 

  25. Inagaki M, Sekimoto S, Tadokoro T et al (2020) Production of 99Mo/99mTc by photonuclear reaction using a natMoO3 target. J Radioanal Nucl Chem 324:681–686. https://doi.org/10.1007/s10967-020-07086-9

    Article  CAS  Google Scholar 

  26. Jang J, Kikunaga H, Sekimoto S et al (2021) Design and testing of a W-MoO3 target system for electron linac production of 99Mo/99mTc. Nucl Instruments Methods Phys Res Sect A Accel Spectrometers, Detect Assoc Equip 987:164815. https://doi.org/10.1016/j.nima.2020.164815

    Article  CAS  Google Scholar 

  27. Müller C, Domnanich KA, Umbricht CA, van der Meulen NP (2018) Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application. Br J Radiol 91:20180074. https://doi.org/10.1259/bjr.20180074

    Article  PubMed  PubMed Central  Google Scholar 

  28. Müller C, Bunka M, Haller S et al (2014) Promising prospects for 44Sc-/47Sc-based theragnostics: application of 47Sc for radionuclide tumor therapy in mice. J Nucl Med 55:1658–1664. https://doi.org/10.2967/jnumed.114.141614

    Article  CAS  PubMed  Google Scholar 

  29. Qaim SM (2015) Nuclear data for medical radionuclides. J Radioanal Nucl Chem 305:233–245. https://doi.org/10.1007/s10967-014-3923-2

    Article  CAS  Google Scholar 

  30. Yagi M, Kondo K (1977) Preparation of carrier-free 47Sc by the 48Ti(γ, p) reaction. Int J Appl Radiat Isot 28:463–468. https://doi.org/10.1016/0020-708X(77)90178-8

    Article  CAS  Google Scholar 

  31. Rane S, Harris JT, Starovoitova VN (2015) 47Ca production for 47Ca/47Sc generator system using electron linacs. Appl Radiat Isot 97:188–192. https://doi.org/10.1016/j.apradiso.2014.12.020

    Article  CAS  PubMed  Google Scholar 

  32. Mamtimin M, Harmon F, Starovoitova VN (2015) Sc-47 production from titanium targets using electron linacs. Appl Radiat Isot 102:1–4. https://doi.org/10.1016/j.apradiso.2015.04.012

    Article  CAS  PubMed  Google Scholar 

  33. Rotsch DA, Brown MA, Nolen JA et al (2018) Electron linear accelerator production and purification of scandium-47 from titanium dioxide targets. Appl Radiat Isot 131:77–82. https://doi.org/10.1016/j.apradiso.2017.11.007

    Article  CAS  PubMed  Google Scholar 

  34. Inagaki M, Sekimoto S, Tanaka W et al (2019) Production of 47Sc, 67Cu, 68Ga, 105Rh, 177Lu, and 188Re using electron linear accelerator. J Radioanal Nucl Chem 322:1703–1709. https://doi.org/10.1007/s10967-019-06904-z

    Article  CAS  Google Scholar 

  35. Loveless CS, Radford LL, Ferran SJ et al (2019) Photonuclear production, chemistry, and in vitro evaluation of the theranostic radionuclide 47Sc. EJNMMI Res. https://doi.org/10.1186/s13550-019-0515-8

    Article  PubMed  PubMed Central  Google Scholar 

  36. Aliev RA, Belyshev SS, Furkina EB et al (2020) Photonuclear production of medically relevant radionuclide 47Sc. J Radioanal Nucl Chem 326:1099–1106. https://doi.org/10.1007/s10967-020-07400-5

    Article  CAS  Google Scholar 

  37. Dikiy NP, Lyashko YV, Shevchenko VA et al (2020) An estimate of 47Sc photonuclear yield in a production target. Probl At Sci Technol 127:158–162

    Google Scholar 

  38. Walshe JM, Potter G (1977) The pattern of the whole body distribution of radioactive copper (67Cu, mCu) in wilson’s disease and various control groups. QJM 46:445–462. https://doi.org/10.1093/oxfordjournals.qjmed.a067518

    Article  CAS  PubMed  Google Scholar 

  39. Novak-Hofer I, Schubiger AP (2002) Copper-67 as a therapeutic nuclide for radioimmunotherapy. Eur J Nucl Med Mol Imaging 29:821–830. https://doi.org/10.1007/s00259-001-0724-y

    Article  CAS  PubMed  Google Scholar 

  40. Qaim SM, Scholten B, Neumaier B (2018) New developments in the production of theranostic pairs of radionuclides. J Radioanal Nucl Chem 318:1493–1509. https://doi.org/10.1007/s10967-018-6238-x

    Article  CAS  Google Scholar 

  41. Marceau N, Kruck TPA, McConnell DB, Aspin N (1970) The production of copper-67 from natural zinc using a linear accelerator. Int J Appl Radiat Isot 21:667–669. https://doi.org/10.1016/0020-708X(70)90121-3

    Article  CAS  PubMed  Google Scholar 

  42. Yagi M, Kondo K (1978) Preparation of carrier-free 67Cu by the 68Zn(γ, p) reaction. Int J Appl Radiat Isot 29:757–759. https://doi.org/10.1016/0020-708X(78)90127-8

    Article  CAS  Google Scholar 

  43. Aizatsky NI, Diky NP, Dovbnya AN et al (2010) 99Mo and 67Cu isotope yields under production conditions of NSC kipt electron accelerator KUT-30. Probl At Sci Technol 2:140–144

    Google Scholar 

  44. Starovoitova V, Foote D, Harris J et al (2013) Cu photonuclear production. AIP Conf Proc 502:19–22. https://doi.org/10.1063/1.3586150

    Article  CAS  Google Scholar 

  45. Gopalakrishna A, Suryanarayana SV, Naik H et al (2018) Production, separation and supply prospects of 67Cu with the development of fast neutron sources and photonuclear technology. Radiochim Acta 106:549–557. https://doi.org/10.1515/ract-2017-2847

    Article  CAS  Google Scholar 

  46. Aliev RA, Belyshev SS, Kuznetsov AA et al (2019) Photonuclear production and radiochemical separation of medically relevant radionuclides: 67Cu. J Radioanal Nucl Chem 321:125–132. https://doi.org/10.1007/s10967-019-06576-9

    Article  CAS  Google Scholar 

  47. Qaim SM (2019) Theranostic radionuclides: recent advances in production methodologies. J Radioanal Nucl Chem 322:1257–1266. https://doi.org/10.1007/s10967-019-06797-y

    Article  CAS  Google Scholar 

  48. Morgenstern A, Apostolidis C, Bruchertseifer F (2020) Supply and clinical application of Actinium-225 and Bismuth-213. Semin Nucl Med 50:119–123. https://doi.org/10.1053/j.semnuclmed.2020.02.003

    Article  PubMed  PubMed Central  Google Scholar 

  49. Qaim SM (2017) Nuclear data for production and medical application of radionuclides: present status and future needs. Nucl Med Biol 44:31–49. https://doi.org/10.1016/j.nucmedbio.2016.08.016

    Article  CAS  PubMed  Google Scholar 

  50. Qaim SM (2012) The present and future of medical radionuclide production. Radiochim Acta 100:635–651. https://doi.org/10.1524/ract.2012.1966

    Article  CAS  Google Scholar 

  51. Aliev RA, Ermolaev SV, Vasiliev AN et al (2014) Isolation of medicine-applicable actinium-225 from thorium targets irradiated by medium-energy protons. Solvent Extr Ion Exch 32:468–477. https://doi.org/10.1080/07366299.2014.896582

    Article  CAS  Google Scholar 

  52. Maslov OD, Sabel’nikov A V., Dmitriev SN, (2006) Preparation of 225Ac by 226Ra(γ, n) photonuclear reaction on an electron accelerator, MT-25 microtron. Radiochemistry 48:195–197. https://doi.org/10.1134/S1066362206020184

    Article  CAS  Google Scholar 

  53. Melville G, Meriarty H, Metcalfe P et al (2007) Production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226. Appl Radiat Isot 65:1014–1022. https://doi.org/10.1016/j.apradiso.2007.03.018

    Article  CAS  PubMed  Google Scholar 

  54. Dash A, Pillai MRA (2010) Knapp FF (2015) Production of 177Lu for targeted radionuclide therapy: available options. Nucl Med Mol Imaging 49:85–107. https://doi.org/10.1007/s13139-014-0315-z

    Article  CAS  Google Scholar 

  55. Liu F, Zhu H, Yu J et al (2017) 68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model. Tumor Biol. https://doi.org/10.1177/1010428317705519

    Article  Google Scholar 

  56. Xu Q, Zhang S, Zhao Y et al (2019) Radiolabeling, quality control, biodistribution, and imaging studies of 177Lu-ibandronate. J Label Compd Radiopharm 62:43–51. https://doi.org/10.1002/jlcr.3694

    Article  CAS  Google Scholar 

  57. Turner JH (2018) Recent advances in theranostics and challenges for the future. Br J Radiol 91:2017–2035. https://doi.org/10.1259/bjr.20170893

    Article  Google Scholar 

  58. Danagulyan AS, Hovhannisyan GH, Bakhshiyan TM et al (2015) Formation of medical radioisotopes 111In, 117mSn, 124Sb, and 177Lu in photonuclear reactions. Phys At Nucl 78:447–452. https://doi.org/10.1134/S1063778815030035

    Article  CAS  Google Scholar 

  59. Kazakov AG, Belyshev SS, Ekatova TY et al (2018) Production of 177Lu by hafnium irradiation using 55-MeV bremsstrahlung photons. J Radioanal Nucl Chem 317:1469–1476. https://doi.org/10.1007/s10967-018-6036-5

    Article  CAS  Google Scholar 

  60. Habs D, Köster U (2011) Production of medical radioisotopes with high specific activity in photonuclear reactions with γ-beams of high intensity and large brilliance. Appl Phys B Lasers Opt 103:501–519. https://doi.org/10.1007/s00340-010-4278-1

    Article  CAS  Google Scholar 

  61. Malinin A, Kurenkov N, Kozlova MSA (1983) Production of radionuclides by photonuclear reactions. III: production of carrier-free indium-111. Radiochem Radioanal Lett 58:213–645

    Google Scholar 

  62. Dallakyan R (2013) Photonuclear production of 111In on the linear electron accelerator. Armen J Phys 6:45–50

    CAS  Google Scholar 

  63. Baljinnyam N, Belov AG, Ganbold G, et al (2008) Possibility of some radionuclides production using high energy electron bremsstrahlung. Preprint of the Joint Institute for Nuclear Research, Dubna. No. E18-2008-119

  64. Ando A, Ando I, Tonami N et al (2000) Production of 105Rh-EDTMP and its bone accumulation. Appl Radiat Isot 52:211–215. https://doi.org/10.1016/S0969-8043(99)00129-3

    Article  CAS  PubMed  Google Scholar 

  65. Feng Y, Phelps TE, Carroll V et al (2017) Chemistry and radiochemistry of As, Re and Rh isotopes relevant to radiopharmaceutical applications: high specific activity radionuclides for imaging and treatment. Dalt Trans 46:14677–14690. https://doi.org/10.1039/c7dt02407j

    Article  CAS  Google Scholar 

  66. Krajewski S, Bilewicz A (2010) The stability of the 105[Rh(16S4diol)Cl2]+ radiopharmaceutical precursor in solutions containing human plasma thiols. J Radioanal Nucl Chem 285:293–300. https://doi.org/10.1007/s10967-010-0577-6

    Article  CAS  Google Scholar 

  67. Velikyan I (2015) 68Ga-based radiopharmaceuticals: production and application relationship. Molecules 20:12913–12943. https://doi.org/10.3390/molecules200712913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Rösch F (2013) Past, present and future of 68Ge/68Ga generators. Appl Radiat Isot 76:24–30. https://doi.org/10.1016/j.apradiso.2012.10.012

    Article  CAS  PubMed  Google Scholar 

  69. Tan HY, Yeong CH, Wong YH et al (2020) Neutron-activated theranostic radionuclides for nuclear medicine. Nucl Med Biol 90–91:55–68. https://doi.org/10.1016/j.nucmedbio.2020.09.005

    Article  CAS  PubMed  Google Scholar 

  70. Jeong JM, Knapp FF (2008) Use of the Oak Ridge National Laboratory Tungsten-188/Rhenium-188 generator for preparation of the Rhenium-188 HDD/Lipiodol Complex for Trans-Arterial Liver Cancer Therapy. Semin Nucl Med. https://doi.org/10.1053/j.semnuclmed.2007.10.003

    Article  PubMed  Google Scholar 

  71. Boschi A, Uccelli L, Pasquali M et al (2014) 188W/188Re generator system and its therapeutic applications. J Chem. https://doi.org/10.1155/2014/529406

    Article  Google Scholar 

  72. IAEA (2021) Medical isotopes production. https://www-nds.iaea.org/relnsd/vcharthtml/MEDVChart.html

Download references

Acknowledgements

This paper was written according to state task of GEOKHI RAS No. 0137–2019–0022.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andrey G. Kazakov.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kazakov, A.G., Ekatova, T.Y. & Babenya, J.S. Photonuclear production of medical radiometals: a review of experimental studies. J Radioanal Nucl Chem 328, 493–505 (2021). https://doi.org/10.1007/s10967-021-07683-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-021-07683-2

Keywords

Navigation