Abstract
Production of high specific activity 186gRe is of interest for development of theranostic radiopharmaceuticals. Previous studies have shown that high specific activity 186gRe can be obtained by cyclotron irradiation of enriched 186W via the 186W(d,2n)186gRe reaction, but most irradiations were conducted at low beam currents and for short durations. In this investigation, enriched 186W metal targets were irradiated at high incident deuteron beam currents to demonstrate production rates and contaminants produced when using thick targets. Full-stopping thick targets, as determined using SRIM, were prepared by uniaxial pressing of powdered natural abundance W metal or 96.86% enriched 186W metal encased between two layers of graphite flakes for target material stabilization. An assessment of structural integrity was made on each target preparation. To assess the performance of graphite-encased thick 186W metal targets, along with the impact of encasing on the separation chemistry, targets were first irradiated using a 22 MeV deuteron beam for 10 min at 10, 20, and 27 μA, with an estimated nominal deuteron energy of 18.7 MeV on the 186W target material (after energy degradation correction from top graphite layer). Gamma-ray spectrometry was performed post EOB on all targets to assess production yields and radionuclidic byproducts. The investigation also evaluated a method to recover and recycle enriched target material from a column isolation procedure. Material composition analyses of target materials, pass-through/wash solutions and recycling process isolates were conducted with SEM, FTIR, XRD, EDS and ICP-MS spectrometry. To demonstrate scaled-up production, a graphite-encased 186W target made from recycled 186W was irradiated for ~2 h with 18.7 MeV deuterons at a beam current of 27 μA to provide 0.90 GBq (24.3 mCi) of 186gRe, decay-corrected to the end of bombardment. ICP-MS analysis of the isolated 186gRe solution provided data that indicated the specific activity of 186gRe in this scaled-up production run was 2.6±0.5 GBq/μg (70±10 Ci/mg).
Acknowledgements
This work was supported the U.S. Department of Energy (DE-SC0007348) and NSERC of Canada Postdoctoral Fellowship (KG). Portions of the materials characterization and product composition analyses were conducted at the University of Washington NanoTech User Facility, a member of the NSF National Nanotechnology Infrastructure Network (NNIN).
References
1. Kelkar, S. S., Reineke, T. M.: Theranostics: combining imaging and therapy. Bioconjugate Chem. 22, 1879 (2011).10.1021/bc200151qSearch in Google Scholar
2. Srivastava, S. C.: Paving the way to personalized medicine: production of some promising theragnostic radionuclides at Brookhaven National Laboratory. Semin. Nucl. Med. 42, 151 (2012).10.1053/j.semnuclmed.2011.12.004Search in Google Scholar PubMed
3. Velikyan, I.: Molecular imaging and radiotherapy: theranostics for personalized patient management. Theranostics 2, 424 (2012).10.7150/thno.4428Search in Google Scholar PubMed
4. Baum, R. P., Kulkarni, H. R.: Theranostics: From molecular imaging using Ga-68 labeled tracers and PET/CT to personalized radionuclide therapy – the Bad Berka experience. Theranostics 2, 437 (2012).10.7150/thno.3645Search in Google Scholar PubMed
5. Das, T., Banerjee, S.: Theranostic applications of lutetium-177 in radionuclide therapy. Curr. Radiopharm. 9, 94 (2016).10.2174/1874471008666150313114644Search in Google Scholar PubMed
6. Milenic, D. E., Brady, E. D., Brechbiel, M. W.: Antibody-targeted radiation cancer therapy. Nat. Rev. Drug Discov. 3, 488 (2004).10.1038/nrd1413Search in Google Scholar PubMed
7. Breitz, H. B., Weiden, P. L., Vanderheyden, J.-L., Appelbaum, J. W., Bjorn, M. J., Fer, M. F., Wolf, S. B., Ratliff, B. A., Seiler, C. A., Foisie, D. C., Fisher, D. R., Schroff, R. W., Fritzberg, A. R., Abrams, P. G.: Clinical experience with rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: results of phase I trials. J. Nucl. Med. 33, 1099 (1992).Search in Google Scholar PubMed
8. Fritzberg, A. R., Meares, C. F.: Metallic Radionuclides in Radioimmunotherapy, Chapter 3. In: P. G. Abrams, A. R. Fritzberg (Eds.), Radioimmunotheapy of Cancer, New York (2000), Marcel Dekker, pp. 57–79.Search in Google Scholar
9. Weiden, P. L., Breitz, H. B., Seiler, C. A., Bjorn, M. J., Ratliff, B. A., Mallett, R., Beaumier, P. L., Appelbaum, J. W., Fritzberg, A. R., Salk, D.: Rhenium-186-Labeled Chimeric Antibody NR-LU-13: Pharmacokinetics, Biodistribution and Immunogenicity Relative to Murine Analog NR-LU-10. J. Nucl. Med. 34, 2111 (1993).Search in Google Scholar PubMed
10. Knapp, F. F., Mirzadeh, S., Beets, A. L.: Reactor production and processing of therapeutic radioisotopes for applications in nuclear medicine. J. Radioanal. Nucl. Chem. 205, 93 (1996).10.1007/BF02040554Search in Google Scholar
11. Moustapha, M. E., Ehrhardt, G. J., Smith, C. J., Szajek, L. P., Eckelman, W. C., Jurisson, S. S.: Preparation of cyclotron-produced 186Re and comparison with reactor-produced 186Re and generator-produced 188Re for the labeling of bombesin. Nuc. Med Biol. 33, 81 (2006).10.1016/j.nucmedbio.2005.09.006Search in Google Scholar
12. Griffiths, G. L., Goldenberg, D. M., Diril, H., Hansen, H. J.: Technetium-99m, rhenium-186, and rhenium-188 direct-labeled antibodies. Cancer 73, 761 (1994).10.1002/1097-0142(19940201)73:3+<761::AID-CNCR2820731303>3.0.CO;2-0Search in Google Scholar PubMed
13. Van Gog, F. B., Visser, G. W. M., Klok, R., Van Der Schors, R., Snow, G. B., Van Dongen, G. A. M. S.: Monoclonal antibodies labeled with rhenium-186 using the MAG3 chelate: relationship between the number of chelated groups and biodistribution characteristics. J. Nucl. Med. 37, 352 (1996).Search in Google Scholar PubMed
14. Ehrhardt, G. J., Blumer, M. E., Su, F. M., Vanderheyden, J. L., Fritzberg, A. R.: Experience with aluminum perrhenate targets for reactor production of high specific activity Re-186. Appl. Radiat. Isot. 48, 1 (1997).10.1016/S0969-8043(96)00124-8Search in Google Scholar
15. Pagel, J. M., Matthews, D. C., Kenoyer, A., Hamlin, D. K., Wilbur, D. S., Fisher, D. R., Gopal, A. K., Lin, Y., Saganic, L., Appelbaum, F. R., Press, O. W.: Pretargeted radioimmunotherapy using anti-CD45 monoclonal antibodies to deliver radiation to murine hematolymphoid tissues and human myeloid leukemia. Cancer Res. 69, 185 (2009).10.1158/0008-5472.CAN-08-2513Search in Google Scholar PubMed
16. Pagel, J. M., Orgun, N., Hamlin, D. K., Wilbur, D. S., Gooley, T. A., Gopal, A. K., Park, S. I., Green, D. J., Lin, Y., Press, O. W.: A comparative analysis of conventional and pretargeted radioimmunotherapy of B-cell lymphomas by targeting CD20, CD22, and HLA-DR singly and in combinations. Blood 113, 4903 (2009).10.1182/blood-2008-11-187401Search in Google Scholar PubMed
17. Green, D. J., Orgun, N. N., Jones, J. C., Hylarides, M. D., Pagel, J. M., Hamlin, D. K., Wilbur, D. S., Lin, Y., Fisher, D. R., Kenoyer, A. L., Frayo, S. L., Gopal, A. K., Orozco, J. J., Gooley, T. A., Wood, B. L., Bensinger, W. I., Press, O. W.: A preclinical model of CD38-pretargeted radioimmunotherapy for plasma cell malignancies. Cancer Res. 74, 1179 (2014).10.1158/0008-5472.CAN-13-1589Search in Google Scholar PubMed
18. Bonardi, M. L., Groppi, F., Manenti, S., Persico, E., Gini, L.: Production study of high specific activity NCA Re-186g by proton and deuteron cyclotron irradiation. Appl. Radiat. Isot. 68, 1595 (2010).10.1016/j.apradiso.2010.03.014Search in Google Scholar PubMed
19. Fassbender, M. E., Ballard, B., Birnbaum, E. R., Engle, J. W., John, K. D., Maassen, J. R., Nortier, F. M., Lenz, J. W., Cutler, C. S., Ketring, A. R., Jurisson, S. S., Wilbur, D. S.: Proton irradiation parameters and chemical separation procedure for the bulk production of high-specific-activity Re-186g using WO3 targets. Radiochimica Acta 101, 339 (2013).10.1524/ract.2013.2031Search in Google Scholar
20. Shigeta, N., Matsuoka, H., Osa, A., Koizumi, M., Izumo, M., Kobayashi, K., Hashimoto, K., Sekine, T., Lambrecht, R. M.: Production method of no-carrier-added Re-186. J. Radioanal. Nucl. Chem. 205, 85 (1996).10.1007/BF02040553Search in Google Scholar
21. Zhang, X. D., Li, W. X., Fang, K. M., He, W. Y., Sheng, R., Ying, D. Z., Hu, W. Q.: Excitation functions for W-nat(p,xn)Re181-186 reactions and production of no-carrier-added Re-186 via W-186(p,n) Re-186 reaction. Radiochimica Acta 86, 11 (1999).10.1524/ract.1999.86.12.11Search in Google Scholar
22. Zhang, X., Li, Q., Li, W., Sheng, R., Shen, S.: Production of no-carrier-added 186Re via deuteron induced reactions on isotopically enriched 186W. Appl. Radiat. Isot. 54, 98 (2001).10.1016/S0969-8043(00)00268-2Search in Google Scholar
23. Alekseev, I. E., Lazarev, V. V.: Cyclotron production and radiochemical isolation of the therapeutic radionuclide 186Re. Radiochemistry 48, 497 (2006).10.1134/S1066362206050171Search in Google Scholar
24. Zhu, Z. H., Wang, X. Y., Wu, Y. H., Liu, Y. F.: An improved Re/W separation protocol for preparation of carrier-free 186Re. J. Radioanal. Nucl. Chem. 221, 199 (1997).10.1007/BF02035266Search in Google Scholar
25. Richards, V. N., Rath, N., Lapi, S. E.: Production and separation of 186gRe from proton bombardment of 186WC. Nucl. Med. Biol. 42, 530 (2015).10.1016/j.nucmedbio.2015.03.001Search in Google Scholar
26. Gott, M. D., Hayes, C. R., Wycoff, D. E., Balkin, E. R., Smith, B. E., Pauzauskie, P. J., Fassbender, M. E., Cutler, C. S., Ketring, A. R., Wilbur, D. S., Jurisson, S. S.: Accelerator-based production of the 99mTc-186Re diagnostic-therapeutic pair using metal disulfide targets (MoS2, WS2, OsS2). Appl. Radiat. Isot. 114, 159 (2016).10.1016/j.apradiso.2016.05.024Search in Google Scholar PubMed
27. Szelecsenyi, F., Steyn, G. F., Kovacs, Z., Aardaneh, K., Vermeulen, C., Van Der Walt, T. N.: Production possibility of Re-186 via the Os-192(p,alpha 3n)Re-186 nuclear reaction. J. Radioanal. Nucl. Chem. 282, 261 (2009).10.1007/s10967-009-0147-ySearch in Google Scholar
28. Hussain, M., Sudar, S., Aslam, M. N., Malik, A. A., Ahmad, R., Qaim, S. M.: Evaluation of charged particle induced reaction cross section data for production of the important therapeutic radionuclide Re-186. Radiochim Acta 98, 385 (2010).10.1524/ract.2010.1733Search in Google Scholar
29. Balkin, E. R., Gagnon, K., Strong, K. T., Smith, B. E., Dorman, E. F., Emery, R. C., Pauzauskie, P. J., Fassbender, M. E., Cutler, C. S., Ketring, A. R., Jurisson, S. S., Wilbur, D. S.: Deuteron irradiation of W and WO3 for production of high specific activity 186Re: Challenges associated with thick target preparation. Appl. Radiat. Isot. 115, 197 (2016).10.1016/j.apradiso.2016.06.021Search in Google Scholar
30. Ziegler, J.: SRIM – The stopping and range of ions in matter. http://www.srim.org/ (2013).Search in Google Scholar
31. Ziegler, J. F., Ziegler, M. D., Biersack, J. P.: SRIM – The stopping and range of ions in matter (2010). Nuclear Instruments & Methods in Physics Research Section B-Beam Interactions with Materials and Atoms 268, 1818 (2010).10.1016/j.nimb.2010.02.091Search in Google Scholar
32. Souza, A. G., Mendes, J., Freire, V. N., Ayala, A. P., Sasaki, J. M., Freire, P. T. C., Melo, F. E. A., Juliao, J. F., Gomes, U. U.: Phase transition in WO3 in microcrystals obtained by sintering process. J. Raman Spectrosc. 32, 695 (2001).10.1002/jrs.727Search in Google Scholar
33. Takacs, S., Szelecsenyi, F., Tarkanyi, F., Sonck, M., Hermanne, A., Shubin, Y., Dityuk, A., Mustafa, M. G., Zhuang, Y. X.: New cross-sections and intercomparison of deuteron monitor reactions on Al, Ti, Fe, Ni and Cu. Nuclear Instruments & Methods in Physics Research Section B-Beam Interactions with Materials and Atoms 174, 235 (2001).10.1016/S0168-583X(00)00589-9Search in Google Scholar
34. Van Gog, F. B., Visser, G. W. M., Stroomer, J. W. G., Roos, J. C., Snow, G. B., Van Dongen, G. A. M. S.: High dose rhenium-186-labeling of monoclonal antibodies for clinical application: pitfalls and solutions. Cancer (Suppl.) 80, 2360 (1997).10.1002/(SICI)1097-0142(19971215)80:12+<2360::AID-CNCR5>3.0.CO;2-FSearch in Google Scholar PubMed
35. Szelecsényi, F., Takacs, S., Tarkanyi, F., Sonck, M., Hermanne, A.: Study of Production Possibility of 186Re Via the 186W(d,2n)186Re nuclear reaction for use in radiotherapy. J. Labl. Compd. Radiopharm. 42, S912 (1999).Search in Google Scholar
36. Qaim, S. M., Tarkanyi, F., Capote R. (Eds.), Charged particle production of 186gRe. In Nuclear Data for the Production of Therapeutic Radionuclides (2011), IAEA Technical Reports Series, No 473, Vienna, Austria, pp. 332–344.Search in Google Scholar
37. Mastren, T., Radchenko, V., Bach, H. T., Balkin, E. R., Birnbaum, E. R., Brugh, M., Engle, J. W., Gott, M. D., Guthrie, J., Hennkens, H. M., John, K. D., Ketring, A. R., Kuchuk, M., Maassen, J. R., Naranjo, C. M., Nortier, F. M., Phelps, T. E., Jurisson, S. S., Wilbur, D. S., Fassbender, M. E.: Bulk production and evaluation of high specific activity 186Re for cancer therapy using enriched 186WO3 targets in a proton beam. Nucl. Med. Biol. 49, 24 (2017).10.1016/j.nucmedbio.2017.02.006Search in Google Scholar
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