Currently, different radiometals are in use for imaging and therapy in nuclear medicine: Ga andIn are examples of nuclides for positron emission tomography (PET) and single photon emission computed tomography (SPECT), respectively, while Lu andAc are used for β- and α-radionuclide therapy. The application of diagnostic and therapeutic radionuclides of the same element (radioisotopes) would utilize chemically-identical radiopharmaceuticals for imaging and subsequent treatment, thereby enabling the radiotheranostic concept. There are two elements which are of particular interest in this regard: Scandium and Terbium. Scandium presents three radioisotopes for theranostic application. Sc (T = 3.9 h) and Sc (T = 4.0 h) can both be used for PET, while Sc (T = 3.35 d) is the therapeutic match-also suitable for SPECT. Currently, Sc is most advanced in terms of production, as well as with pre-clinical investigations, and has already been employed in proof-of-concept studies in patients. Even though the production ofSc may be more challenging, it would be advantageous due to the absence of high-energetic γ-ray emission. The development of Sc is still in its infancy, however, its therapeutic potential has been demonstrated preclinically. Terbium is unique in that it represents four medically-interesting radioisotopes.Tb (T = 5.32 d) and Tb (T = 17.5 h) can be used for SPECT and PET, respectively. Both radioisotopes were produced and tested preclinically. Tb has been the first Tb isotope that was tested (asTb-DOTATOC) in a patient. Both radionuclides may be of interest for dosimetry purposes prior to the application of radiolanthanide therapy. The decay properties of Tb (T = 6.89 d) are similar to Lu, but the coemission of Auger electrons make it attractive for a combined β/Auger electron therapy, which was shown to be effective in preclinical experiments. Tb (T = 4.1 h) has been proposed for targeted α-therapy with the possibility of PET imaging. In terms of production, Tb andTb are most promising to be made available at the large quantities suitable for future clinical translation. This review article is dedicated to the production routes, the methods of separating the radioisotopes from the target material, preclinical investigations and clinical proof-of-concept studies of Sc and Tb radionuclides. The availability, challenges of production and first (pre)clinical application, as well as the potential of these novel radionuclides for future application in nuclear medicine, are discussed.

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BackgroundRadiotheragnostics 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.ResultsUp 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.ConclusionThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s41181-017-0024-x) contains supplementary material, which is available to authorized users.