(47)Sc 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, (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. METHODS: (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. RESULTS: 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. CONCLUSION: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s41181-017-0024-x) contains supplementary material, which is available to authorized users.