Reactor production of Thorium-229

https://doi.org/10.1016/j.apradiso.2016.05.002Get rights and content

Highlights

  • Production of 229Th from irradiation of 226Ra, 228Ra, and 227Ac is studied.

  • Microgram quantities irradiated under high neutron flux for varying durations.

  • Measured radionuclide yields lower than predicted but generally in uncertainty range.

  • ORNL 229Th reserve can be increased by 450 MBq per gram of irradiated 226Ra.

  • Large 227Ra cross section further results in production of 228Ra.

Abstract

Limited availability of 229Th for clinical applications of 213Bi necessitates investigation of alternative production routes. In reactor production, 229Th is produced from neutron transmutation of 226Ra, 228Ra, 227Ac and 228Th. Irradiations of 226Ra, 228Ra, and 227Ac targets at the Oak Ridge National Laboratory High Flux Isotope Reactor result in yields of 229Th at 26 days of 74.0±7.4 MBq/g, 260±10 MBq/g, and 1200±50 MBq/g, respectively. Intermediate radionuclide yields and cross sections are also studied.

Introduction

A large number of antibody targeted radiopharmaceuticals are in development for the treatment of blood-borne cancers, disseminated cancers and a variety of solid tumors using alpha-emitters such as 213Bi, 225Ac, 223Ra, 227Th and 211At (Miederer et al., 2008; Kim and Brechbiel, 2012). The alpha emitters combine high-potency, high-linear energy transfer, and low toxicity; consequently, the initial attempts to use alpha particles from alpha emitting radioisotopes have focused on leukemia and small micrometastatic deposits of cancer cells such as lymphoma. Among possible alpha emitters for application in targeted alpha therapy (TAT), interest in 225Ac (t1/2=10.0 days) has increased substantially since the initial supply of this radioisotope from Oak Ridge National Laboratory (ORNL) in 1997 (Boll et al., 2005a, Du et al., 20032002, Mirzadeh, 19981996). Since then, ORNL has been the main supplier of high-purity 225Ac from decay of existing 229Th stock, and since 2011 ~26 GBq of 225Ac has been harvested annually from the 229Th stock, typically in six campaigns per year. Supply of 225Ac, however, remains inadequate to meet the demand if current or planned clinical studies are found to be effective. Furthermore, the success of 223Ra for treatment of metastatic prostate cancer, as the first alpha-emitting radiopharmaceutical approved by the U. S. Food and Drug Administration (Colletti, 2013), will further encourage the research and development (R&D) of other alpha-emitting radiopharmaceutical therapies, including 225Ac, for clinical use. Efforts to increase the current production of 225Ac and evaluate alternate production routes have been considered a high priority (Nuclear Science Advisory Committee, 2015), and in recent years a significant investment has been made in R&D aimed at increasing the supply of 225Ac (Mirzadeh, 2013, Jost et al., 2012, Weidner et al., 2012a, Weidner et al., 2012b, Zhuikov et al., 2011; Apostolidis et al., 2005a, Apostolidis et al., 2005b).

In this work, we report on a systematic evaluation of production of 229Th via neutron irradiation of 226Ra, 227Ac, and 228Ra targets in the ORNL High Flux Isotope Reactor (HFIR), examining the nuclear reactions involved in multiple production pathways and assessing the future capacity for reactor supply of 229Th. Some preliminary data from this research were presented earlier (Boll et al., 2005b).

Production of 229Th through neutron irradiation of 226Ra requires three neutron captures and two β decays through a number of pathways, shown in Fig. 1 along with their associated nuclear data.

From the nuclear data presented in Fig. 1, it can be seen that the dominant production pathway is via:

R226a(n,γ)R227a(β)A227c(n,γ)A228c(β)T228h(n,γ)T229h.

The amount of 229Th produced from irradiation of 226Ra can be calculated by solving a linked set of Bateman equations (Bateman, 1910) of the form shown in (1), (2).Ni(t)=k=1i(j=ki1Λj)Nk0j=kiajeΛjtaj=mj(ΛmΛj)1(m=k,k+1,,i),where

Λi1 is the formation rate constant (λi−1 or σi−1ϕ) of the ith species from the (i−1)th species.

Λi is the total depletion rate constant (λiiϕ) of the ith species.

Throughout this paper, these equations are solved using a Java tool, “IsoChain” (Almanza et al., 2006, Mirzadeh and Walsh, 1997), using the nuclear data given in Fig. 1, and the previously measured neutron fluxes in the HFIR hydraulic tube facility, listed in Table 1 (Mahmood et al., 1995). In this table and in all future references, the thermal to epithermal ratio, R, refers to the ratio of the thermal flux to the flux in the energy range 0.5 eV and 0.1 MeV divided by the logarithm of the energy difference of that energy range, which is known as the flux per unit lethargy.R=φthφep/ln(EUpperElower)

In our computation, any unknown cross sections are assigned a value of 1 barn.

Section snippets

Estimating isotope yields, sensitivities and uncertainties

An initial calculation was performed to assess the potential for production of 229Th from 226Ra using a thermal neutron flux of 2.0×1015 n cm−2 s−1 and a thermal to epithermal flux ratio of 25, representing the neutron flux in a typical target irradiation position near the mid-plane of the HFIR. This calculation was performed for 12 time steps of 25 days irradiation, with 35 days of decay between each time step, which is representative of ~two years' (12 cycles') worth of irradiation in HFIR. The

Radioactivity and mass measurements

Radioactivity measurement was performed by γ-ray spectroscopy. Samples were assayed at a distance of 5–121 cm from a calibrated solid-state high-purity Ge detector (50 cm3, EG&G Ortec, Oak Ridge, Tenn) coupled to a PC-based multi-channel analyzer (MCA) employing GENIE software (Canberra Industries, Inc., Meriden, Conn.). The detector has a resolution of 1.0 keV at 123 keV and 1.8 keV at 1332 keV. Energy and efficiency calibrations were determined with γ-ray sources traceable to the National Institute

Evaluation of primary 229Th production chain

As discussed in Section 1, the primary production pathway for formation of 229Th is via three neutron capture reactions and two β decays through formation of the 227Ac and 228Th intermediate radionuclides.

A. 226Ra [n,γ]227Ra (t1/2=42.2 m, β) 227Ac reaction.

This reaction proceeds through formation of 227Ra, which quickly decays to 227Ac. Examination of 227Ac production from 226Ra was performed for the thirteen 226Ra targets listed in Table 3. The yields of 227Ac are given as the activity per µg

Discussion

As discussed in the previous sections, for one HFIR cycle (~26 days), the yields of 229Th from 226Ra and 227Ac targets are 74.0±7.4 MBq/g and 1200±50 MBq/g, respectively. For the 226Ra target, the ratio of measured to predicted yield was 0.54±0.19, and for the 227Ac target this ratio was 0.56±0.10. The yield of 229Th from 228Ra in a single measurement was 260±10 MBq/g, which is only ~24% of the expected yield. Large absorption in 227Ra will result in lower than expected 229Th yields if the

Acknowledgements

The ORNL Reactor Division, in particular Mr. G. Hirtz for his assistance related to the irradiation planning and scheduling is acknowledged with appreciation. The authors acknowledge Dr. Roy Copping and Dr. Steve Sherman for their critical review of the manuscript.

This research is supported by the Isotope Program, Office of Nuclear Physics of the U.S. Department of Energy. ORNL is managed by UT-Battelle, LLC, for the U.S. Department of Energy under contract DE-AC05-00OR22725.

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