VALIDATION OF HCl-EtOH-Method FOR PRECONCENTRATION OF ~(68)Ge/~(68)Ga GENERATOR ELUATE AND STUDY OF THE SORPTION-DESORPTION MECHANISM

摘要

The chemical form of ~(68)Ga in the eluate from a ~(68)Ge/~(68)Ga generator implies that it can be directly used as a versatile source of ~(68)Ga for the synthesis of radiopharmaceuticals (RPs) applying an appropriate chelating agent. Long-term experience of ~(68)Ge/~(68)Ga generator application by various research groups indicates that the presence of non-isotopic carrier and parent radionuclide in the eluate remains a major challenge. Burnazyan FMBC, Russia, has developed new technologies to implement a high yield purification and concentration of ~(68)Ga generator eluate in a very short time (15 min or less). This process needs no using any carrier, toxic organic compounds and strong acids. Ion exchange technologies developed provide ~(68)Ga concentrated solutions of high chemical and radiochemical purity in the form of 0.02-0.1 M HCl solution (with ~(68)Ga yield of ＞ 98 %, corrected for decay). These solutions have been successfully applied for labeling various BCA-conjugated biomolecules (DOTA-TATE, DOTA-Afp~7, DOTA-lysine-octreotide, etc). Both these methods are based on a combined cation-anion exchange in mixed solution media (HCl-acetone or HCl-ethanol). Note, that these new conditions allow to achieve an efficient transfer of Ga from a cation exchanger to an anion exchanger at a concentration of HCl well below 2.5M. After that ~(68)Ga is eluted from the anion-exchange resin with 0.02 - 0.1 M hydrochloric acid. Both methods are patented. Acetone method is not used yet because of its several drawbacks, while ethanol method was tested out in several models of tubing-technology module. Chemical and radiochemical purity, stability and reproducibility of the method is confirmed by various methods (pH, GC , ICP, TLC) in a large series of experiments. Currently, the new cassette module (with disposable sterile cassettes) is under development. It was found that it is exactly an addition of organic solvent that allows to substantially decrease the HCl concentrations without degrading the efficiency of the whole process. In order to understand the Ga speciation in solutions as a function of composition, which determines its ion-exchange behavior, we measured Ga K-edge EXAFS/XANES spectra. The X-ray abosprion spectra were acquired at the "Structural Materials Science" beamline of the Kurchatov Synchrotron Radiation Center in the fluorescence mode. A few series of solution samples (GaCl_3 5 mmol in 0.1-3 M HCl) were studied. In each series, the concentration of ethanol was varied from 0 % to 90 %. In each series of samples, an abrupt change in the XANES spectrum was observed above a certain threshold concentration of ethanol. This change is due to transformation of Ga coordination from octahedral [Ga(H_2O)6]~(3+) to tetrahedral [GaCl_4]~-. It was also found that a higher concentration of hydrochloric acid gives rise to a lower concentration of alcohol required to induce such a transition. XANES conclusions are supported by ab initio spectral simulations as well as by quantitative analysis of EXAFS data. As a result of a large series of experiments with different concentrations of HCl and EtOH, the EXAFS data confirm the optimality of selected conditions. These spectroscopic data can be used to rationally tune the ion-exchange behavior of Ga.