Question 12.9.Q2: Some 40 million nuclear medicine imaging procedures are carr......

(a) Of the two nuclear reactor based Mo-99 production techniques, the HEU fission technique, in comparison with Mo-98 neutron activation technique, is by far the prevalent technique, mainly because it provides Mo-99 with a significantly higher specific activity. Another advantage of the uranium fission technique is that, concurrently with Mo-99, it produces other fission products, such as iodine-131, that can be used in nuclear medicine.
However, the U-235 fission technique is characterized by two serious disadvantages in comparison with the Mo-98 neutron activation technique: (1) Security issue related to the use of highly enriched (weapons grade) uranium-235 for non-military purposes and (2) Production of radioactive waste. We note that Mo-98 activation, in contrast to HEU fission, is not associated with any extraordinary security concerns nor does it produce any radioactive waste.
Both techniques are reactor based, so that as far as the Mo-99 supply chain is concerned both techniques suffer similar problems. There are only a few nuclear reactors around the world (all of them of advanced age and close to end-of-life) that have additional facilities required for production of Mo-99 radionuclide using HEU targets. Therefore, migration of Mo-99 production from nuclear reactors to other non-reactor based techniques is a long-term goal that to date has been discussed at great lengths but has not yet been realized.

(b) The most serious concern with regard to the production of Mo-99 with the HEU fission technique is that the process involves the use of weapons-grade HEU, presenting a significant security risk related to nuclear proliferation stemming from production, transport, and use of HEU for non-military purpose. This leads to increased pressure to discontinue civilian use of HEU in favor of much safer natural uranium or, preferably, depleted uranium as target material for Mo-99 production in nuclear reactors.
Of course, migration from HEU to depleted uranium would only alleviate the HEU security problem while the problem of aging nuclear reactors and production of radioactive waste in the form of fission fragments would still be present.
Radioactive waste generated in Mo-99 production is of concern since Mo-99 appears in HEU target as fission fragment characterized with a branching ratio of only 6.1 %. Most often, all other fragments produced in the target are discarded as radioactive waste, highlighting the question of disposal and storage of long-lived radioactive waste for generations to come.
The security issue related to HEU targets as well as problems with radioactive waste and aging nuclear reactors are stimulating serious proposals for devising Mo-99 production techniques based on particle accelerators rather than on nuclear reactors. Most of these techniques have been known for years; however, developing them for large-scale clinical Mo-99 production is neither simple nor inexpensive.

Several promising nuclear reactions are under consideration. Electron accelerators as well as proton and heavier ion machines have been considered as possible alternative means for Mo-99 production, but no concrete practical solutions have been developed to date.
Some of these innovative techniques, aimed at dispensing with use of HEU targets, are as follows:

(1) High-power electron linear accelerators (linacs) producing bremsstrahlung xray beams in bremsstrahlung targets can be considered as potential source of high intensity photon beam used either in: (i) photonuclear (photodisintegration) reaction on Mo-100 through the reaction { }_{42}^{100} \mathrm{Mo}(\gamma, \mathrm{n}){ }_{42}^{99} \mathrm{Mo} or (ii) photofission reaction on uranium-238.
Both the photodisintegration and photo-fission techniques are feasible but require very high intensity x-ray beams that are not yet readily available. Moreover, the electron accelerator, be it a high-energy linac or a microtron, must produce a photon beam spectrum with peak energy exceeding the threshold for (i) photonuclear reaction and (ii) photo-fission, respectively.
The Mo-99 branching ratio in photo-fission of U-238 is about 6 % just like in regular neutron triggered U-235 fission; however, the cross section of photo-fission in contrast to regular fission is over two orders of magnitude lower, requiring very high intensity photon beams. The major advantage of photo-fission is that it bypasses the need for nuclear reactor and that it is based on readily available U-238 (in natural uranium or in depleted uranium). Thus, no highly enriched U-235 would be required, but the problem of production and disposal of radioactive waste in the form of fission products would remain.
(2) Proton accelerators generating protons that bombard high atomic number targets to produce neutrons can be used as source of neutrons for (i) neutron activation of Mo-98 targets or (ii) nuclear fission of U-235 targets, similar to the current nuclear reactor based Mo-99 production techniques. This would solve the problem with aging nuclear reactors; however, it would not alleviate the problem of nuclear waste produced in U-235 targets.
(3) Deuteron accelerators generating deuterons striking a low atomic number target (tritium or carbon) to produce fast neutrons could be used to bombard enriched Mo-100 targets with fast neutrons to trigger the following neutron activation reaction: { }_{42}^{100} \mathrm{Mo}(\mathrm{n}, 2 \mathrm{n}){ }_{42}^{99} \mathrm{Mo}. Advantage of this technique would be that production of radioactive waste would be very small.
(4) Another possibility under consideration for Mo-99 production is bombardment of zirconium-96 (Zr-96) target with energetic α particles obtained by accelerating { }_2^4 \mathrm{He} nuclei (α particles) in an accelerator. While α particle accelerators are available, it is not clear whether or not they can provide sufficiently high currents to enable an efficient production of Mo-99 through the nuclear reaction { }_{40}^{96} \mathrm{Zr}(\alpha, n){ }_{42}^{99} \mathrm{Mo}. Of course, the α particle kinetic energy must exceed the threshold kinetic energy of the nuclear reaction (see Prob. 270).

(5) Also considered is direct production of Tc-99m based on nuclear reaction { }_{42}^{100} \mathrm{Mo}(p, 2n){ }_{42}^{99m} \mathrm{Tc} triggered with protons from a cyclotron bombarding a Mo-100 target. This approach would bypass the intermediate step of Mo-99 production that is used in all currently employed or investigated options for Tc-99m production.

This direct solution is feasible, however, since Tc-99m would be produced directly rather than through the intermediate Mo-99 step, the short Tc-99m half-life would preclude the shipping of Tc-99m to sites remote from the cyclotron. Thus, the user would have to produce Tc-99m on-site and only a few medical centers around the world would be capable of implementing this approach because of the large cost involved in purchasing and operating a cyclotron just for the purpose of Tc-99m production. We should note, however, that this approach has the added attraction of not producing radioactive waste associated with reactor based nuclear fission in uranium targets as well as with linac based photo-fission in uranium targets. Moreover, around the world there already is a hospital-installed base of cyclotrons for producing fluorine-18 radionuclide for positron emission studies. Many of these machines could be used for production of Tc-99m in the future.

(c) The techniques for Mo-99 production, discussed in (b), are summarized in Table 12.34. In contrast to the two current techniques for Mo-99 production both based on nuclear reactors, Table 12.34 presents 6 possible techniques using a variety of reaction targets (Mo-98, Mo-100, U-235, and Zr-96) as well as four different particle accelerators:

(1) Two techniques use high energy electron linear accelerators (linacs) to produce high energy x rays which are used to induce: (1) photodisintegration [(γ, n) reaction] of a Mo-100 target into Mo-99 radionuclide and (2) photofission of U-238 target producing fission fragment Mo-99 among many other fission fragments.
(2) Two techniques use proton accelerators to produce neutrons which can be used to induce: (1) neutron activation in a Mo-98 target or (2) nuclear fission in a U-235 target. The two techniques are similar to the currently used reactor based techniques except that neutron projectiles originate in a particle accelerator rather than in a nuclear reactor. Like in a nuclear reactor, the result of neutron bombardment of Mo-98 or U-235 targets results in production of the Mo-99 radionuclide and uranium targets produce radioactive waste that must be dealt with appropriately.
(3) The fifth technique uses neutrons produced in a deuteron accelerator and bombards a Mo-100 target to produce Mo-99 through a (n, 2n) nuclear reaction.
(4) The sixth technique uses energetic α particles from a particle accelerator to bombard Zr-96 to produce the Mo-99 radionuclide.