A theoretical model for the production of Ac-225 for cancer therapy by neutron capture transmutation of Ra-226

Abstract

Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation by bombarding Ra-226 with high-energy neutrons from a neutron source to produce Ra-225 and hence Ac-225, which can be used as a generator to produce Bi-213 for use in ‘Targeted Alpha Therapy’ for cancer.

This paper examines the possibility of producing Ac-225 by neutron capture using a theoretical model in which neutron energy is convoluted with the corresponding neutron cross sections of Ra-226. The total integrated yield can then be obtained.

This study shows that an intense beam of high-energy neutrons could initiate neutron capture on Ra-226 to produce Ra-225 and hence practical amounts of Ac-225 and a useful reduction of Ra-226.

Introduction

Ac-225 is an alpha emitting radioisotope with a 10 day half life that decays to produce Bi-213. Either Ac-225 or Bi-213 can be used as an agent for radio-immunotherapy (Allen et al., 2004).

Alpha particle emitters are the most potent sources for lethal irradiation of single cancer cells and micrometastases because of their densely ionising radiation. Alpha particles are of considerable interest for radio-immunotherapy applications since their short range in soft tissue is limited to only a few cell diameters.

The Bi-213 radioisotope is of special interest because of its unique nuclear properties, which include a short 46-minute half-life, high-energy (8.4 MeV) alpha-particle emission and can be conjugated with molecular carriers. Furthermore, the Ac-225/Bi-213 generator and the chemistry of the associated radionuclides are well understood allowing for the various separations.

At present, Ac-225 has been obtained from the natural radioactive decay of Ra-225, the decay product of Th-229, which is itself obtained from decay of U-233. Th-229 has a long half-life of 7340 years, thus, only a very small fraction is converted to Ac-225 and Bi-213 during a one-year period limiting its natural availability to researchers. This means if larger amounts of Ac-225 are needed it must be artificially produced.

There are a number of artificial ways to produce Ac-225 (Koch et al.,1997). They are:

• ²³²Th (n; γ, 2β) ²³³U

  This method involves bombarding of Th-232 with thermal neutrons to produce U-233, which will then follow the U-233 decay chain leading to Ac-225. Although Th-232 has a reasonably high neutron cross section, this method is very impractical since, as mentioned above, both U-233 and its decay product Th-229 have a long half-life thus severely limiting the supply of Ac-225, which is further down the decay chain.

• ²²⁶Ra (3n; 2β) ²²⁹Th

  This method involves bombarding of radium with thermal neutrons to produce Th-229 after 3 neutron capture events, which decays to Ac-225. The process is not simple and involves several intermediate steps. Again this method will only lead to a limited amount of Ac-225 for the same reasons previously mentioned.

• ²²⁶Ra (p; 2n) ²²⁵Ac

  In this method protons from a cyclotron produce Ac-225 directly with the peak cross section being about 540 mb at 16 MeV proton energy. The ²²⁶Ra (p; 3n) ²²⁴Ac reaction rapidly takes over at higher energies.

  Much of the work involving cyclotron production (Morgenstern, 2006) of Ac-225 has been carried out by the ITU in Karlsruhe, Germany, where the feasibility of producing Ac-225 by proton irradiation of Ra-226 in a cyclotron through the reaction Ra-226(p, 2n)Ac-225 was experimentally demonstrated. Proton energies varied from 8.8 MeV to 24.8 MeV and cross-sections were determined by radiochemical analysis of reaction yields. Maximum yields were reached at incident proton energies of 16.8 MeV.

  Radiochemical separation of Ac-225 from the irradiated target yielded a product suitable for targeted alpha therapy of cancer as reported by Morgenstern.

  The main goal of their work was to investigate the feasibility of large-scale production of Ac-225, that is, in the mCi range. The irradiation of 30.1 mg Ra-226 with 15.9 MeV protons for 45.3 h at 50 μA current, yielded 484.7 MBq (13.1 mCi) of Ac-225 and showed the feasibility of large-scale production of Ac-225.

• ²²⁶Ra (γ; n) ²²⁵Ra

  This reaction produces Ra-225 (half-life: 14.9 days), which subsequently decays to Ac-225 (half-life: 10 days). A theoretical model (Melville et al., 2006) showed how much Ra-225 could be produced and this was in reasonable agreement with experiments (Melville et al., 2007) carried out using a linac as a gamma source. However, the low experimental production rate of 407 kBq (11 μCi) of Ra-225/h/20 mCi of Ra-226 as reported by Melville et al. (2007) is far too low to be of practical use. Further research (Melville and Allen, 2009) showed how the quantity of Ra-225 could be increased and this was compared to the (p, 2n) reaction above.

More recently (2012), very promising research at Los Alamos has indicated that Ac-225 and Ra-223 can be produced in commercial quantities using very high energy accelerator driven protons to irradiate natural thorium. Yield estimates of multi-Curie quantities of Ac-225 and Ra-223 being produced in a single 10-day irradiation have been reported (Weidner et al., 2012).

Another possible way of producing Ra-225 is:

$${}^{226}\mathbf{R}\mathbf{a}\mathbf{(}n;2n){}^{225}\mathbf{R}\mathbf{a}$$

This reaction produces Ra-225 through high-energy neutron bombardment, which subsequently decays to Ac-225.

This process will be the basis of this research paper.

While each of these methods eventually results in a supply of Ac-225 for use in a Bi-213 generator, they all require additional chemical processing and/or separation steps that are still being investigated and will likely increase production costs.

The purpose of this paper is to construct a theoretical model for the production of Ra-225 using neutron capture for the transmutation of Ra-226.

A summary of relevant data for important radionuclides is shown in Table 1.