Untersuchung kationenselektiver Extraktionssäulen zur Konzeption nuklearmedizinischer Radionuklidgeneratoren

The topic of the present work is the conception of a Yttrium-90 radionuclide generator for nuclear medicine applications. Due to its physical properties Y-90 is considered as one of the most useful nuclides for radiotherapeutic cancer treatment. The parent nuclide Strontium-90 is gained during reprocessing of fission products. Thus, the sustained availability of large quantities of Y-90 is limited to a number of research facilities. A radionuclide generator provides an independent Y-90 source and enhances the capacities for radiopharmaceutical research and biomedical applications. The present work focussed on the identification of appropriate column materials for the separation of Strontium and Yttrium. The results for two materials are reported: AnaLig® Sr-01 and crystalline antimonic acid. Based on the mode of operation of the Technetium-99m generator the aim was to enable the construction of a compact, enclosed apparatus. The projected device comprises a reservoir for the eluant, the ion-exchange column, pipings and radiation shielding. Elution of Y-90 could then be easily performed by connecting evacuated vials to the outlet tube. The prospected concept involves physical and chemical confinements that exclude most of the known processes for Strontium-Yttrium separation. For example no ligands, no oxidizing reactants (e.g. nitric acid) and no organic solvents are to be used, but small volumes of isotonic or buffer solutions and dilute acids respectively. AnaLig® Sr-01 is a commercially available resin used in extraction chromatography. Its high selectivity for Strontium cations results from the strictly defined cavity of the imbedded cryptand. Determination of weight distribution coefficients, elution studies and pre-generator experiments were carried out. Quantitative separation of Yttrium from Strontium and Zirconium is possible using small volumes of 0,05 M hydrochloric acid as eluant. Furthermore, high flow rates were achieved. The low acid concentration of the eluate is advantageous for its further processing with biomolecules. In a pre-generator experiment a small Strontium breakthrough was observed. However, the required separation factors of 106 can be achieved by combining two columns in a row. All obtained results indicate AnaLig® Sr-01 to be the optimum choice as a column material in a Sr/Y-90 generator. As no strong radiation source was available the effect of high doses on the material could not be examined. The activities needed for therapeutic purposes exceeding those of diagnostic applications by several orders of magnitude all materials in an Y-90 generator have to sustain high radiation doses. Thus, radiation stability is the crucial aspect of a prospected column material. Due to its complex structure of covalent bonds AnaLig® Sr-01 is to be estimated as extremely susceptible to radiation damage. Utilization of AnaLig® Sr-01 would imply deviating from the initial concept. If Sr-90 is removed from the column and stored in a reservoir after each elution of Y-90 the exposure time of the resin would be minimized. In this case the system would require additional reservoirs, branched tubings, radioactive waste containers and peristaltic pumps. However, implementation of the radionuclide generator as an enclosed, low-maintenace apparatus is hardly feasible. Since inorganic materials exhibit much higher radiolytic stability than organic extractants, further investigations concentrated on an inorganic ion exchanger. Crystalline antimonic acid is well known for its high selectivity and capacity for Strontium cations. Crystalline antimonic acid was prepared through hydrolysis of antimony pentachloride and further treatment of the precipitate. Using radioactive Antimony-125 as an internal standard enables non-destructive analysis of chemical characteristics such as solubility and column bleeding. As in the case of AnaLig® Sr-01, hydrochloric acid was chosen as eluant. In batch experiments 1 M hydrochloric acid was determined as appropriate eluant: Under these conditions the adsorption of Strontium and Zirconium on crystalline antimonic acid is quantitative while Yttrium is very slightly adsorbed and can be eluted. However, transfering the results from batch experiments to column studies was not possible: periodic elution of a column loaded with Sr-90/Y-90 results in less than 1% of the expected yield of Y-90. This discrepancy was assumed to be caused by changes in crystal structure due to the continuous contact with the eluant. For example, the loss of water of crystallization would result in a contraction of the cavities obstracting the mobility of smaller cations. To further investigate possible aging processes different samples of crystalline antimonic acid were prepared through suspension and re-crystallization respectively. The comparison of X-ray data and weight distribution coefficients of the samples was expected to faciliate correlation between water content and ion exchange behavior. The changes in lattice parameters and cation selectivity caused by different kinds of treatment are contradictory, though. In addition to aging processes another possible influence was discussed: in batch experiments solvated Yttrium cations were brought into contact with crystalline antimonic acid whereas in the column experiment Y-90 ions originate from the decay of Sr-90 nuclei trapped within the lattice. However, according to ion exchange theory no such deviance should arise from different initial conditions. Because of its unsteady ion exchange properties in elution studies the use of crystalline antimonic acid in an Y-90 generator is not possible.