Production of actinium-225 from a (n,p) reaction: Feasibility and pre-design studies

Fouad A. Abolaban; Essam M. Banoqitah; Eslam M. Taha; Abdulsalam M. Alhawsawi; Fathi A. Djouider; Andrew Nisbet

doi:10.2478/nuka-2021-0008

Abstract

Actinium-225 is used in nuclear medicine for the treatment of malignant tumours. It can be applied to produce Bi-213 in a reusable generator or can be used alone as an agent for radiation therapy, in particular for targeted alpha therapy. However, the availability of Ac-225 for worldwide use, particularly in low- and middle-income countries, is limited. We present a feasibility study employing GATE, an open-source Monte Carlo simulation toolkit, on the production of Ac-225 from a neutron generator. This work suggests that a design consisting of three concentric cylinders, the innermost a Cf-252 neutron source, the middle nickel cylinder acting as a proton-producing target and the outer cylinder a RaCl₂ target may provide a feasible design outline for an Ac-225 generator.

References

Villers, A., & Grosclaude, P. (2008). Épidémiologie du cancer de la prostate. Med. Nucl., 32(1), 2–4. DOI: 10.1016/j.mednuc.2007.11.003.
Open DOI Search in Google Scholar Back to article
Global Cancer Observatory. (2019). Prostate 2018. Available from https://gco.iarc.fr/today/data/fact-sheets/cancers/27-Prostate-fact-sheet.pdf.
Search in Google Scholar Back to article
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 68(6), 394–424. DOI: 10.3322/caac.21492.
Open DOI Search in Google Scholar Back to article
Davison, B. J., Gleave, M. E., Goldenberg, S. L., Degner, L. F., Hoffart, D., & Berkowitz, J. (2002). Assessing information and decision preferences of men with prostate cancer and their partners. Cancer Nurs., 25(1), 42–49.
Search in Google Scholar Back to article
Hofman, M. S., Violet, J., Hicks, R. J., Ferdinandus, J., Thang, S. P., Akhurst, T., Iravani, A., Kong, G., Kumar, A. R., Murphy, D. G., Eu, P., Jackson, P., Scalzo, M., Williams, S. G., & Sandhu, S. (2018). [177 Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol., 19(6), 825–833. DOI: 10.1016/S1470-2045(18)30198-0.
Open DOI Search in Google Scholar Back to article
Li, Y., Tian, Z., Rizvi, S., Bander, N., Allen, B., & Wales, S. (2002). In vitro and preclinical targeted alpha therapy of human prostate cancer with Bi-213 labeled J591 antibody against the prostate specific membrane antigen. Prostate Cancer Prostatic Dis., 5, 36–46. DOI: 10.1038/sj/pcan/4500543.
Open DOI Search in Google Scholar Back to article
Azorín-Vega, E., Rojas-Calderón, E., Ferro-Flores, G., Aranda-Lara, L., Jiménez-Mancilla, N., & Nava-Cabrera, M. A. (2019). Assessment of the radiation absorbed dose produced by 177 Lu-iPSMA, 225 AciPSMA and 223 RaCl2 to prostate cancer cell nuclei in a bone microenvironment model. Appl. Radiat. Isot., 146, 66–71. DOI: 10.1016/j.apradiso.2019.01.020.
Open DOI Search in Google Scholar Back to article
Ahn, J., Park, S., Zuniga, B., Bera, A., Song, C. S., & Chatterjee, B. (2016). Vitamin D in prostate cancer. In Vitamins and hormones (Vol. 100, pp. 321–355). New York: Academic Press Inc.
Search in Google Scholar Back to article
Ludwig, D. L., Bryan, R. A., Dawicki, W., Geoghegan, E. M., Liang, Q., Gokhale, M., Reddy, V., Garg, R., Allen, K. J. H., Berger, M. S., & Dadachova, E. (2020). Preclinical development of an actinium-225-labeled antibody radio-conjugate directed against CD45 for targeted conditioning and radioimmunotherapy. Biol. Blood Marrow Transplant., 26(3), S160–S161. DOI: 10.1016/j.bbmt.2019.12.714.
Open DOI Search in Google Scholar Back to article
Miederer, M., Scheinberg, D. A., & McDevitt, M. R. (2008). Realizing the potential of the actinium-225 radionuclide generator in targeted alpha particle therapy applications. Adv. Drug Deliv. Rev., 60(12), 1371–1382.
Search in Google Scholar Back to article
Dekempeneer, Y., Keyaerts, M., Krasniqi, A., Puttemans, J., Muyldermans, S., Lahoutte, T., D’huyvetter, M., & Devoogdt, N. (2016). Targeted alpha therapy using short-lived alpha-particles and the promise of nanobodies as targeting vehicle. Expert Opin. Biol. Ther., 16(8), 1035–1047. DOI: 10.1080/14712598.2016.1185412.
Open DOI Search in Google Scholar Back to article
Morgenstern, A., Apostolidis, C., & Bruchertseifer, F. (2020). Supply and clinical application of actinium-225 and bismuth-213. Semin. Nucl. Med., 50(2), 119–123. DOI: 10.1053/j.semnuclmed.2020.02.003.
Open DOI Search in Google Scholar Back to article
Artun, O. (2017). Estimation of the production of medical Ac-225 on thorium material via proton accelerator. Appl. Radiat. Isot., 127, 166–172. DOI: 10.1016/j.apradiso.2017.06.006.
Open DOI Search in Google Scholar Back to article
Kossert, K., Takács, M. P., & Nähle, O. (2020). Determination of the activity of ²²⁵Ac and of the half-lives of ²¹³Po and ²²⁵Ac. Appl. Radiat. Isot., 156, 109020. DOI: 10.1016/j.apradiso.2019.109020.
Open DOI Search in Google Scholar Back to article
Bruchertseifer, F., Kellerbauer, A., Malmbeck, R., & Morgenstern, A. (2019). Targeted alpha therapy with bismuth-213 and actinium-225: Meeting future demand. J. Label. Compd. Radiopharm., 62(11), 794–802. DOI: 10.1002/jlcr.3792.
Open DOI Search in Google Scholar Back to article
Allen, B. J. (2017). A comparative evaluation of Ac225 vs Bi213 as therapeutic radioisotopes for targeted alpha therapy for cancer. Australas. Phys. Eng. Sci. Med., 40(2), 369–376. DOI: 10.1007/s13246-017-0534-6.
Open DOI Search in Google Scholar Back to article
Ruddy, F. H., Dulloo, A. R., Seidel, J. G., & Petrović, B. (2004). Separation of the alpha-emitting radioisotopes actinium-225 and bismuth-213 from thorium-229 using alpha recoil methods. Nucl. Instrum. Methods Phys. Res. Sect. B: Beam Interact. Mater. Atoms, 213, 351–356. DOI: 10.1016/S0168-583X(03)01580-5.
Open DOI Search in Google Scholar Back to article
Artun, O. (2017). Estimation of the production of medical Ac-225 on thorium material via proton accelerator. Appl. Radiat. Isot., 127, 166–172. DOI: 10.1016/j.apradiso.2017.06.006.
Open DOI Search in Google Scholar Back to article
Apostolidis, C., Molinet, R., McGinley, J., Abbas, K., Möllenbeck, J., & Morgenstern, A. (2005). Cyclotron production of Ac-225 for targeted alpha therapy. Appl. Radiat. Isot., 62(3), 383–387. DOI: 10.1016/j.apradiso.2004.06.013.
Open DOI Search in Google Scholar Back to article
Jan, S., Santin, G., Strul, D., Staelens, S., Assie, K., Autret, D., Avner, S., Barbier, R., Bardies, M., Bloomfield, P. M., Brasse, D., Breton, V., Bruyndonckx, P., Buvat, I., Chatziioannou, A. F., Choi, Y., Chung, Y. H., Comtat, C., Donnarieix, D., Ferrer, L., Glick, S. J., Groiselle, C. J., Guez, D., Honore, P. F., Kerhoas-Cavata, S., Kirov, A. S., Kohli, V., Koole, M., Krieguer, M., van der Laan, D. J., Lamare, F., Largeron, G., Lartizien, C., Lazaro, D., Maas, M. C., Maigne, L., Mayet, L., Melot, F., Merheb, C., Pennacchio, E., Perez, J., Pietrzyk, U., Rannou, F. R., Rey, M., Schaart, D. R., Schmidtlein, C. R., Simon, L., Song, T. Y., Vieira, J. M., Visvikis, D., Van der Walle, R., Wieers, E., & Morel, C. (2004). GATE: a simulation toolkit for PET and SPECT. Phys. Med. Biol., 49(19), 4543–4561. DOI: 10.1088/0031-9155/49/19/007.
Open DOI Search in Google Scholar Back to article
Grevillot, L., Bertrand, D., Dessy, F., Freud, N., & Sarrut, D. (2011). A Monte Carlo pencil beam scanning model for proton treatment plan simulation using GATE/GEANT4. Phys. Med. Biol., 56(16), 5203–5219. DOI: 10.1088/0031-9155/56/16/008.
Open DOI Search in Google Scholar Back to article
Grevillot, L., Boersma, D. J., Fuchs, H., Aitkenhead, A., Elia, A., Bolsa, M., Winterhalter, C., Vidal, M., Jan, S., Pietrzyk, U., Maigne, L., & Sarrut, D. (2020). Technical Note: GATE-RTion: a GATE/Geant4 release for clinical applications in scanned ion beam therapy. Med. Phys., 47(8), 3675–3681. DOI: 10.1002/mp.14242.
Open DOI Search in Google Scholar Back to article
Aitelcadi, Z., Toufique, Y., El Kharrim, A., Elmadani, S., Hilali, A., & Bouhali, O. (2018). Validation of the GATE Monte Carlo code for radiation therapy: Varian Clinac2300C/D. In Proceedings of the 2018 International Conference on Optimization and Applications, ICOA 2018, 31 May 2018, pp. 1–4. Institute of Electrical and Electronics Engineers Inc. DOI: 10.1109/ICOA.2018.8370602.
Open DOI Search in Google Scholar Back to article
Aguiar, P., Casarejos, E., Silva-Rodriguez, J., Vilan, J. A., & Iglesias, A. (2015). Geant4-GATE simulation of a large plastic scintillator for muon radiography. IEEE Trans. Nucl. Sci., 62(3), 1233–1238. DOI: 10.1109/TNS.2015.2431297.
Open DOI Search in Google Scholar Back to article
Lamare, F., Turzo, A., Bizais, Y., Le Rest, C. C., & Visvikis, D. (2006). Validation of a Monte Carlo simulation of the Philips Allegro/GEMINI PET systems using GATE. Phys. Med. Biol., 51(4), 943–962. DOI: 10.1088/0031-9155/51/4/013.
Open DOI Search in Google Scholar Back to article
Papadimitroulas, P. (2017). Dosimetry applications in GATE Monte Carlo toolkit. Phys. Medica, 41, 136–140. DOI: 10.1016/j.ejmp.2017.02.005.
Open DOI Search in Google Scholar Back to article
Thiam, C. O., Breton, V., Donnarieix, D., Habib, B., & Maigne, L. (2008). Validation of a dose deposited by low-energy photons using GATE/GEANT4. Phys. Med. Biol., 53(11), 3039–3055. DOI: 10.1088/0031-9155/53/11/019.
Open DOI Search in Google Scholar Back to article
Villoing, D., Marcatili, S., Garcia, M.-P., & Bardiès, M. (2017). Internal dosimetry with the Monte Carlo code GATE: validation using the ICRP/ICRU female reference computational model. Phys. Med. Biol., 62(5), 1885–1904. DOI: 10.1088/1361-6560/62/5/1885.
Open DOI Search in Google Scholar Back to article
Geant4 Collaboration. (2018). Physics reference manual. CERN.
Search in Google Scholar Back to article
Maslov, O. D., Sabel’nikov, A. V., & Dmitriev, S. N. (2006). Preparation of ²²⁵Ac by ²²⁶Ra(γ,n) photonuclear reaction on an electron accelerator, MT-25 microtron. Radiochemistry, 48(2), 195–197. DOI: 10.1134/S1066362206020184.
Open DOI Search in Google Scholar Back to article
Balasundar, S., Chandrasekaran, S., Subramanian, V., & Venkatraman, B. (2021). Investigations on neutron attenuation properties of poly-boron materials using Am-Be and ²⁵²Cf sources neutron spectra. Ann. Nucl. Energy, 153, 108083. DOI: 10.1016/j.anucene.2020.108083.
Open DOI Search in Google Scholar Back to article

Production of actinium-225 from a (n,p) reaction: Feasibility and pre-design studies

Abstract

Paradigm

My account