Calcium targets for production of the medical Sc radioisotopes in reactions with p, d or α projectiles

The scandium radioisotopes for medical application can be produced in reactions of calcium with proton, deuteron or alpha projectiles. Enriched isotopic calcium material is commercially available mainly as calcium carbonate which can be used directly for production of Sc radioisotopes or can be converted into other calcium compounds or into metallic form. The superiority of application of calcium oxide is shown throughout analysis of use of each target chemical form.


Introduction
Majority of medically interested radioisotopes are produced in reactions induced by neutrons i.e. in reactors. Nevertheless, the alternative methods of their production are being extensively developed. The advantages and drawbacks of each production route are well presented by M. A. Synowiecki et al in [1].
The studies on the alternative methods were triggered by unplanned shut-downs of reactors several years ago which caused the shortage of isotopes (i.e. 99 Tc) widely used in medical applications. These studies are also stimulated by development of the diagnostic techniques and by search for replacements having longer half-live then isotopes recently used in PET scanning. One of the alternative method of these radioisotopes production is use of the reactions induced by accelerated projectiles such as protons, deuterons or alpha particles.
Majority of the studies on the scandium isotopes production via reactions induced by p, d or α projectiles are performed using calcium as a target nucleus. The alternative nucleus is Ti as the source of Sc isotopes but comparison of the cross sections for reactions of both nuclei (Table 1) shows that reaction with Ca nucleus promises much higher production efficiency. As can be found from these data production of 43 Sc with very high efficiency can be achieved even applying target composed of the natural calcium employing reaction of 40 Ca (96.94 % of nat. abundance) with α particles [3].  (-) Unstable in air , quick manipulation is required or best to be handled in the inert atmosphere.
Ca (-) Have to be prepared by CaCO3 conversion; it is a two steps procedure; (-) unstable in the air, it requires handling in the inert atmosphere.
under the beam (-) Thermal insulator; Decomposes producing CaO+CO2. The target cracks when exposed to intensive beams due to this process (see Fig. 1); (-) Production of large amount of 13 N (decaying in ~10 min via β + to 13 C).
(-) If not sufficient cooling can melt in the beam.
Treatment after irradiation (+) Dissolves very easily in a weak acids.
(+) Dissolves easily in a weak acids; only slightly more difficult than carbonate.
Efficiency see next table

Chemical form of the target
Production of the Sc medical radioisotopes in reaction of Ca nucleus can be done working with unprocessed enriched material i.e. with calcium carbonate (CaCO3, the chemical form of the enriched Ca isotopes mostly available commercially) or with material converted into either calcium oxide (CaO) or metal (Ca). Work with each target form has advantages and drawbacks ( Table  2). The thermal damages mentioned in Table 2 for calcium carbonate can be eliminated by mixing the target material with a good heat conductor e.g. graphite or aluminium as discussed in [5]. The activity of the Sc radioisotopes produced during the same time of irradiation of Ca metallic target would be nearly tripled comparing to activity produced while using CaCO3 (or doubled if working with CaO). This is due to the number of nuclei per cm 2 (N) in targets with thicknesses covering the projectile range in CaCO3, CaO and Ca. The ratio of nuclei numbers in these targets is ~ 1:2:3, respectively, and thus is the produced activity. Av -Avogadro constant = 6.022140857×10 23 mol −1 ; * calculated using SRIM 2013 code; ** example energy for 43 Sc isotope production in 40 Ca reaction with α; However, conversion of CaCO3 into metallic Ca is a time-consuming two steps reduction process [6,7]. The process can be done under vacuum by decomposing carbonate to oxide, followed by the oxide reduction into Ca using metallic (Me) reductants such as e.g. Zr, Ti.
CaCO3  CaO + CO2 (heating at temp. > 700 ºC) (2) 2CaO + Me  Ca + MeO (reduction) In addition, process may as well introduce additional contaminants to the target apart from those present in the available starting material. Also the process efficiency (lower than 80%) has to be kept in mind considering metallic target. Therefore, it is better to avoid this conversion if it's not vital.
Working with metallic Ca would also require a special vacuum containers and/or construction of a transfer vacuum line to the cyclotron to prevent the contact of Ca with air.
Taking these difficulties into account it is much better to work with calcium oxide as target. Although activity produced is only doubled comparing to activity produced with CaCO3 target of adequate thickness (see Table 3) but conversion to CaO is much easier than conversion to Ca. It can be done either by heating the oxide in flow of the inert gas [8] or in vacuum using the resistant heating. The advantages of the second method are: the instant/online control on the decomposition process via controlling the vacuum and gives the possibility of cooling down the produced CaO in the air free atmosphere. Conversion carried in a special vessel/crucible with the perforated cover (Fig. 2.) and venting-in the vacuum apparatus after completion of the procedure, with inert gas allows the transfer of the produced CaO to the glove box for manipulations needed to produce the final target (e.g. pressing the pellet, encapsulating into container, etc.) without special precautions. In addition decrease of the oxygen content in the target results in a significant decrease of the side radioactivity in the irradiation area related to the production of 13 N in 16 O(p,x) 13 N or 16 O(d,x) 13 N reaction.
The oxide targets prepared as inserts into graphite bed as described in [5] survived 45 min irradiation with 15 µA proton beam very well. There were no signs of thermal damage of the target. The irradiation conditions are sufficient to produce ~8 GBq of 44g Sc irradiating the CaO converted from enriched up to 99.2 % 44 CaCO3. Taking into account the activity loses during isotope separation and labelling process, such amount of 44 Sc should be enough for diagnosing ~ 75 patients (the estimation based on clinical studies for 44 Sc [9] where 50.5 MBq of 44 Sc-PSMA-617 were applied for single diagnosis).

Conclusions
Production of the research quantities of Sc radioisotopes can easily be performed using targets made directly from calcium carbonate. However, for clinical application when higher activities are required more favourable is to work with targets made from calcium oxide.
Conversion of carbonate into oxide is one step process practically without loses of the often expensive, enriched calcium material.
As it has been shown using the calcium oxide instead of carbonate gives nearly double activity within the same time of irradiation and much less undesirable radioactivity (originating from decay of 13 N formed in the side reaction) is produced in the irradiation area.