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Background: 124I Iodine (T 1 / 2 = 4.18 d) is the only long-life positron emitter radioisotope of iodine that may be used for both imaging and therapy as well as for 131I dosimetry. Its physical characteristics permits taking advantages of the higher Positron Emission Tomography (PET) image quality, whereas the availability of new molecules to be targeted with 124I makes it a novel innovative radiotracer probe for a specific molecular targeting. Results: In this study Monte Carlo and SRIM/TRIM modelling was applied to predict the nuclear parameters of the 124I production process in a small medical cyclotron IBA 18/9 Cyclone. The simulation production yields for 124I and the polluting radioisotopes were calculated for the natural and enriched 124TeO2 + Al2O3 solid targets irradiated with 14.8 MeV protons. The proton beam was degraded energetically from 18 MeV with 0.2 mm Havar foil. The 124Te(p,xn)124I reactions were taken into account in the simulations. The optimal thickness of the target material was calculated using the SRIM/TRIM and Geant4 codes. The results of the simulations were compared with the experimental data obtained for the natural TeO2 +Al2O3 target. The dry distillation technique of the 124-iodine was applied. Conclusions: The experimental efficiency for the natural Te target was better than 41% with an average thick target (>0.8 mm) yield of 1.32 MBq/μAh. Joining the Monte Carlo and experimental approaches makes it possible to optimize the methodology for the 124I production from the expensive Te enriched targets. [ABSTRACT FROM AUTHOR]