Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application

Currently, different radiometals are in use for imaging and therapy in nuclear medicine: (68)Ga and (111)In are examples of nuclides for positron emission tomography (PET) and single photon emission computed tomography (SPECT), respectively, while (177)Lu and (225)Ac 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. (43)Sc (T(1/2) = 3.9 h) and (44)Sc (T(1/2) = 4.0 h) can both be used for PET, while (47)Sc (T(1/2) = 3.35 d) is the therapeutic match—also suitable for SPECT. Currently, (44)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 of (43)Sc may be more challenging, it would be advantageous due to the absence of high-energetic γ-ray emission. The development of (47)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. (155)Tb (T(1/2) = 5.32 d) and (152)Tb (T(1/2) = 17.5 h) can be used for SPECT and PET, respectively. Both radioisotopes were produced and tested preclinically. (152)Tb has been the first Tb isotope that was tested (as (152)Tb-DOTATOC) in a patient. Both radionuclides may be of interest for dosimetry purposes prior to the application of radiolanthanide therapy. The decay properties of (161)Tb (T(1/2) = 6.89 d) are similar to (177)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. (149)Tb (T(1/2) = 4.1 h) has been proposed for targeted α-therapy with the possibility of PET imaging. In terms of production, (161)Tb and (155)Tb 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.