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.