47Sc as useful β–-emitter for the radiotheragnostic paradigm: a comparative study of feasible production routes

Background Radiotheragnostics makes use of the same molecular targeting vectors, labeled either with a diagnostic or therapeutic radionuclide, ideally of the same chemical element. The matched pair of scandium radionuclides, 44Sc and 47Sc, satisfies the desired physical aspects for PET imaging and radionuclide therapy, respectively. While the production and application of 44Sc was extensively studied, 47Sc is still in its infancy. The aim of the present study was, therefore, to investigate and compare two different methods of 47Sc production, based on the neutron irradiation of enriched 46Ca and 47Ti targets, respectively. Methods 47Sc was produced by thermal neutron irradiation of enriched 46Ca targets via the 46Ca(n,γ)47Ca → 47Sc nuclear reaction and by fast neutron irradiation of 47Ti targets via the 47Ti(n,p)47Sc nuclear reaction, respectively. The product was compared with regard to yield and radionuclidic purity. The chemical separation of 47Sc was optimized in order to obtain a product of sufficient quality determined by labeling experiments using DOTANOC. Finally, preclinical SPECT/CT experiments were performed in tumor-bearing mice and compared with the PET image of the 44Sc labeled counterpart. Results Up to 2 GBq 47Sc was produced by thermal neutron irradiation of enriched 46Ca targets. The optimized chemical isolation of 47Sc from the target material allowed formulation of up to 1.5 GBq 47Sc with high radionuclidic purity (>99.99%) in a small volume (~700 μL) useful for labeling purposes. Three consecutive separations were possible by isolating the in-grown 47Sc from the 46/47Ca-containing fraction. 47Sc produced by fast neutron irradiated 47Ti targets resulted in a reduced radionuclidic purity (99.95-88.5%). The chemical purity of the separated 47Sc was determined by radiolabeling experiments using DOTANOC achievable at specific activities of 10 MBq/nmol. In vivo the 47Sc-DOTANOC performed equal to 44Sc-DOTANOC as determined by nuclear imaging. Conclusion The production of 47Sc via the 46Ca(n,γ)47Ca nuclear reaction demonstrated significant advantages over the 47Ti production route, as it provided higher quantities of a radionuclidically pure product. The subsequent decay of 47Ca enabled the repeated separation of the 47Sc daughter nuclide from the 47Ca parent nuclide. Based on the results obtained from this work, 47Sc shows potential to be produced in suitable quality for clinical application.