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

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, 44 Sc and 47 Sc, satisfies the desired physical aspects for PET imaging and radionuclide therapy, respectively. While the production and application of 44 Sc was extensively studied, 47 Sc is still in its infancy. The aim of the present study was, therefore, to investigate and compare two different methods of 47 Sc production, based on the neutron irradiation of enriched 46 Ca and 47 Ti targets, respectively. 47 Sc was produced by thermal neutron irradiation of enriched 46 Ca targets via the 46 Ca(n,γ) 47 Ca → 47 Sc nuclear reaction and by fast neutron irradiation of 47 Ti targets via the 47 Ti(n,p) 47 Sc nuclear reaction, respectively. The product was compared with regard to yield and radionuclidic purity. The chemical separation of 47 Sc 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 44 Sc labeled counterpart. Up to 2 GBq 47 Sc was produced by thermal neutron irradiation of enriched 46 Ca targets. The optimized chemical isolation of 47 Sc from the target material allowed formulation of up to 1.5 GBq 47 Sc 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 47 Sc from the 46/47 Ca-containing fraction. 47 Sc produced by fast neutron irradiated 47 Ti targets resulted in a reduced radionuclidic purity (99.95–88.5%). The chemical purity of the separated 47 Sc was determined by radiolabeling experiments using DOTANOC achievable at specific activities of 10 MBq/nmol. In vivo the 47 Sc-DOTANOC performed equal to 44 Sc-DOTANOC as determined by nuclear imaging. The production of 47 Sc via the 46 Ca(n,γ) 47 Ca nuclear reaction demonstrated significant advantages over the 47 Ti production route, as it provided higher quantities of a radionuclidically pure product. The subsequent decay of 47 Ca enabled the repeated separation of the 47 Sc daughter nuclide from the 47 Ca parent nuclide. Based on the results obtained from this work, 47 Sc shows potential to be produced in suitable quality for clinical application.