Production of Zr-89 radioisotope using a variable energy cyclotron (TR-19)

Introduction. The increasing number of nuclear medicine procedures employing radiolabelled targeting agents demand the use of radioisotopes with longer half-lives (usually within hours and days). Such radioisotope is ⁸⁹Zr, which is an emergent radioisotope with potential use in the field of PET imaging. Its decay properties (t_1/2 = 78.41 h, EC = 76.6%, β+ = 22.3%, E_max(β⁺) = 897 keV, E_ave.(β⁺) = 396.9 keV, R_ave.(β⁺) = 1.18 mm, E_γ = 908.97 keV, I_γ = 100%) make it suitable for the design of novel radiotracers, such as nanoparticules and monoclonal antibodies (mAb). Therefore, many ⁸⁹ZR-radiolabelled PET agents are currently under development, in different stages, aiming to obtain better targeting agents for various types of cancer. This work presents our experience in the field of production of ⁸⁹Zr at TR-19 cyclotron and further radiochemical processing to obtain pharmaceutical grade ⁸⁹Zr-oxalate. Methods. ⁸⁹Zr was obtained by irradiation of _natY foils (99.9%, Alpha Aesar) at TR-19 cyclotron by ^natY(p,n)⁸⁹Zr nuclear reaction with following parameters: I=25 μA; t=4h. The protons were extracted at 14.2 MeV and degraded for optimal cross-section to 12.7 MeV when reaching the target, by using a pure aluminium degrader. After irradiation, the target was dissolved using 2M HCl followed by light heating (60˚C) until the solution became clear. The obtained ⁸⁹ZrCl₄ solution was passed on a ZR1-R10-S cartridge (Triskem) were zirconium ions were trapped. The recovery of zirconium was carried out with 0.5 M oxalic acid. Quality control of the final product was carried out. Irradiation yield, radiolabelling yield, pH, radiochemical purity and radionuclide purity were assessed. Results. Using the semi-automated solid target system, 1.28 GBq ⁸⁹ZrCl₄ were obtained, while with the fully-automated solid target system, 2.7 GBq. The yield after irradiation and processing the target using fully-automated solid target system was 71.8%. The radiochemical purity, assessed by radio-HPLC, was higher than 99% after purification. Conclusions. The characteristics of the [⁸⁹Zr]ZrCl4 solution meet the requirements for the biomolecules radiolabelling (antibodies) and comply to the translation to radiopharmaceutical production line, aiming to develop new generation of PET agents for preclinical testing and clinical trials. (author)