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AbstractAbstract
[en] For more than fifty years, the long-lived 68Ge/68Ga generators have been in development, obtaining 68Ga without the need of having in house cyclotron, which is a considerable convenience for PET centers that have no nearby cyclotrons. 68Ga decays 89% by positron emission and low photon emission (1077 keV) and the physical half life of 67.7 minutes is compatible with the pharmacokinetics of low biomolecular weight substances like peptides and antibody fragments. Moreover, its established metallic chemistry allows it to be stably bound to the carrier peptide sequence via a suitable bifunctional chelator, such as DOTA. All these reasons together with the technology of PET/CT allowed advances in molecular imaging, in particular in the diagnosis of neuroendocrine diseases. However, the eluate from the commercial 68Ge/68Ga generators still contains high levels of long lived 68Ge, besides other metallic impurities, which competes with 68Ga with a consequent reduction of the labeling yield of biomolecules, such as Fe3+ and Zn2+. Thus, the lower the amount of impurities in the eluate, the competition between the radiolabeled and unlabeled peptide by the receptor will be smaller and the quality of imaging will be better, a subsequent purification step is needed after the generator elution. The aim of this work is to evaluate different purifications methods of 68Ga to label biomolecules, with emphasis on the study of the chemical impurities contained in the eluate and to develop a new purification method. Several purification methods were studied. Many cationic resin were tested simulating the commercial process. 68Ga is adsorbed in cationic resin, which is not commercial available and eluted in acid/acetone solution. The use of minor particles of cationic resin AG50W-X4 (200-400 mesh) showed the best results. An innovate method was the extraction chromatography, which is based on the absorption of diisopropyl ether in XAD 16 and 68Ga recovery in deionized water. Although the results regarding to 68Ga recovery and the radiochemical separation between 68Ga and 65Zn were excellent, there was no reproducibility on the purification of metals. The most promising and innovative method was the 68Ga purification performed by cationic resin in basic media, which presented the best results, especially regarding the Zn reduction (98 ± 2)%, the chemical contaminant found in great abundance in 68Ga eluate. The total impurities reduction was (95 ± 4)%. The peptides DOTATOC/DOTATATE were labeled 68Ga in three different forms: purified 68Ga in basic solution, through solvent extraction and no purified 68Ga. The best result was achieved with DOTATATE labeling with purified 68Ga in basic media, proving the purification process efficiency. (author)
Original Title
Desenvolvimento de metodos de purificacao do 67Ga e 68Ga para a marcacao de biomoleculas
Primary Subject
Source
2012; 149 p; Thesis (Ph.D.)
Record Type
Miscellaneous
Literature Type
Thesis/Dissertation
Report Number
Country of publication
BETA DECAY RADIOISOTOPES, BETA-PLUS DECAY RADIOISOTOPES, CHARGED PARTICLES, CHROMATOGRAPHY, DAYS LIVING RADIOISOTOPES, DRUGS, ELECTRON CAPTURE RADIOISOTOPES, EVEN-EVEN NUCLEI, EVEN-ODD NUCLEI, GALLIUM ISOTOPES, GERMANIUM ISOTOPES, HOURS LIVING RADIOISOTOPES, INTERMEDIATE MASS NUCLEI, IONS, ISOTOPES, LABELLED COMPOUNDS, MATERIALS, NUCLEI, ODD-EVEN NUCLEI, ODD-ODD NUCLEI, ORGANIC COMPOUNDS, ORGANIC POLYMERS, PETROCHEMICALS, PETROLEUM PRODUCTS, POLYMERS, RADIOACTIVE MATERIALS, RADIOISOTOPES, SEPARATION PROCESSES, ZINC ISOTOPES
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