This work describes the first real developments in radiochemistry around exotic radionuclides at the cyclotron of Orléans focusing on the radiochemistry of two radiometals 165 Er and 52 Mn. For these developments, targets were irradiated during 0.5-2 h at a maximum current of 2 µA. All activities have been determined by radiotracer method. The production of 165 Er from a natural Ho target that was irradiated is described. Higher activities of 165 Er were obtained via deuteron irradiation then proton with lower ratio 165 Er/ 166 Ho (400/1 to 8/1). By using LN2 resin, the separation of adjacent lanthanides was made on various concentrations of HNO 3 (0.3 to 5 M). Weight coefficients (Dw) were defined in a batch test. Then, the first tests of separation on a semi-automated system were made: the ratio 166+nat Ho/ 165 Er in an isolated fraction was significantly reduced (1294 ± 1183 (n = 3)) but the reliability and reproducibility of the system must be improved. Then, a new Cr powder-based target for 52 Mn production was designed. Its physical aspects such as mechanics, thermal resistance and porosity have been studied. Dw for various compositions of eluent Ethanol/HCl were evaluated by reducing contact time (1 h) comparative to the literature. A first evaluation of semi-automated separation Cr/Mn has been made.Instruments 2018, 2, 15 2 of 23 cyclotron of Orléans is of interest in producing radionuclides for analytical applications allowing for the validation of the separation by the radiotracer method [9] and a method as sensitive as Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). In this context, it was necessary to initiate tools and methodology in radiochemistry to develop further the accelerator in the area of medical radionuclides. However, two constraints relative to the choice of radionuclides were met at the cyclotron of Orléans. The first constraint was to produce gamma emission and the second was that the half-life of the radionuclide produced must be below 100 days (due to nuclear waste management considerations). Hence for the following work, we used 165 Er/Er, 166 Ho/Ho, 51 Cr/Cr and 52 Mn/Mn. Other tools to improve radiochemical separation based on resins, methodology, and target design must be developed. Two cases hereafter illustrate the method's development for the production and subsequent separation of 165 Er and 52 Mn.Instruments 2018, 3, 15 2 of 22 radionuclides for analytical applications allowing for the validation of the separation by the radiotracer method [9] and a method as sensitive as Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). In this context, it was necessary to initiate tools and methodology in radiochemistry to develop further the accelerator in the area of medical radionuclides. However, two constraints relative to the choice of radionuclides were met at the cyclotron of Orléans. The first constraint was to produce gamma emission and the second was that the half-life of the radionuclide produced must be below 100 days (due to nuclear waste management considerations)...