44 Sc is a promising β + -emitter for molecular imaging with intermediate half-life of 4 h. Due to the chemical similarity of Sc 3+ to the Lu 3+ and Y 3+ cations, 44 Sc-DOTA bioconjugates are expected to demonstrate similar properties in vivo as the 177 Lu-and 90 Y-bioconjugates, what is important in planning the radionuclide therapy. 44 Sc can be obtained from the 44 Ti/ 44 Sc generator. An alternative method for 44 Sc production can be the irradiation of 44 Ca target at small cyclotrons. The aim of our work was to optimize the parameters of 44 CaCO 3 irradiation and to develop a simple procedure for 44 Sc separation from the calcium target. For optimization study, 44 CaCO 3 targets were irradiated by protons in the energy range of 5.6-17.5 MeV with 9 MeV being found to be the best energy for 44 Ca irradiations. A simple and fast separation procedure of 44 Sc from calcium target was developed using chelating resin Chelex 100. DOTATATE conjugate was successfully radiolabelled with high yield at elevated temperature using the produced 44 Sc. While 44 CaCO 3 is relatively expensive, the cost of 44 Sc-DOTATATE production can be reduced by target recovery. Due to low proton energy required to produce GBq activity level of 44 Sc, the availability of 44 Sc radioisotope could be enhanced to open new opportunities for applications in medical imaging.

BackgroundRecently, significant interest in 44Sc as a tracer for positron emission tomography (PET) imaging has been observed. Unfortunately, the co-emission by 44Sc of high-energy γ rays (Eγ = 1157, 1499 keV) causes a dangerous increase of the radiation dose to the patients and clinical staff. However, it is possible to produce another radionuclide of scandium—43Sc—having properties similar to 44Sc but is characterized by much lower energy of the concurrent gamma emissions. This work presents the production route of 43Sc by α irradiation of natural calcium, its separation and purification processes, and the labeling of [DOTA,Tyr3] octreotate (DOTATATE) bioconjugate.MethodsNatural CaCO3 and enriched [40Ca]CaCO3 were irradiated with alpha particles for 1 h in an energy range of 14.8–30 MeV at a beam current of 0.5 or 0.25 μA. In order to find the optimum method for the separation of 43Sc from irradiated calcium targets, three processes previously developed for 44Sc were tested. Radiolabeling experiments were performed with DOTATATE radiobioconjugate, and the stability of the obtained 43Sc-DOTATATE was tested in human serum.ResultsStudies of natCaCO3 target irradiation by alpha particles show that the optimum alpha particle energies are in the range of 24–27 MeV, giving 102 MBq/μA/h of 43Sc radioactivity which creates the opportunity to produce several GBq of 43Sc. The separation experiments performed indicate that, as with 44Sc, due to the simplicity of the operations and because of the chemical purity of the 43Sc obtained, the best separation process is when UTEVA resin is used. The DOTATATE conjugate was labeled by the obtained 43Sc with a yield >98 % at elevated temperature.ConclusionsTens of GBq activities of 43Sc of high radionuclidic purity can be obtainable for clinical applications by irradiation of natural calcium with an alpha beam.

The aim of this study was to evaluate acyclic ligands which can be applied for labeling proteins such as monoclonal antibodies and their fragments with scandium radionuclides. Recently, scandium isotopes (47Sc, 44Sc) are more available and their properties are convenient for radiotherapy or PET imaging. They can be used together as “matched pair” in theranostic approach. Because proteins denaturize at temperature above 42 °C, ligands which efficiently form complexes at room temperature, are necessary for labelling such biomolecules. For complexation of scandium radionuclides open chain ligands DTPA, HBED, BAPTA, EGTA, TTHA and deferoxamine have been chosen. We found that the ligands studied (except HBED) form strong complexes within 10 min and that the radiolabelling yield varies between 96 and 99 %. The complexes were stable in isotonic NaCl, but stability of 46Sc-TTHA, 46Sc-BAPTA and 46Sc-HBED in PBS buffer was low, due to formation by Sc3+stronger complexes with phosphates than with the studied ligands. From the radiolabelling studies with n.c.a. 47Sc we can conclude that the most stable complexes are formed by the 8-dentate DTPA and EGTA ligands.

The short half-life of 212 Bi and 213 Bi limits the application of these radionuclides in a radionuclide therapy.

Scandium radionuclides / Sc-47 radiobioconjugates / Radionuclide therapy Summary. Radionuclides with medium energy beta emission and a several day half-life are attractive candidates for radioimmunotherapy. Among the most promising in this category is 47 Sc produced by fast neutron irradiation (E n > 1 MeV) of titanium target with high energy neutrons in 47 Ti(n, p) 47 Sc nuclear reaction. In the previously reported production scheme the dissolution of the TiO 2 target in hot concentrated H 2 SO 4 and evaporation of the resulting solution were the most timeconsuming steps. The present paper describes new, simple and efficient production method of 47 Sc, where the slow dissolution of the target is avoided. After irradiation in fast neutron flux 47 TiO 2 and Li 2 47 TiF 6 targets were dissolved in HF solutions. Next 47 Sc was separated from the target using anion exchange resin Dowex 1 with 0.4 M HF + 0.06 M HNO 3 solution as eluent. The eluted 47 Sc was adsorbed on cation exchange resin and eluted with 0.5 M of ammonium acetate. The 47 Sc separation yield in the proposed procedure is about 90% with the separation time less than 2 h. The obtained nocarrier-added 47 Sc was used to label DOTATATE conjugate with 96% labeling yield.