| Summary: | 碩士 === 國立清華大學 === 原子科學系 === 89 === Abstract
C-aryl derivatives of DOTA (N,N’,N”,N’”-tetrakis(carboxymethyl)- 1,4,7,10-tetraazacyclododecane) were synthesized by a novel template reductive reaction. Reaction of triethylenetetraamine with ferric chloride generated previously a Fe(Ⅲ) templated diimine complex. For cyclococondensation, the diimine complex was subsequently reacted with aryl pyruvaldehyde. Aryl cyclen was obtained after adding sodium borohydride to reduce the cyclic imine and simultaneously remove the iron via conversion of Fe(Ⅲ) to Fe(Ⅱ). Actually the synthetic process was an one-pot reaction, proceeding without separation of any intermediate or transition state product. Further reaction of the acryl cyclen obtained with tert-Butyl-bromoacetate or 2-bromoacetamide could generate the derivatives of DOTA.
67GaCl3 or 68GaCl3 was taken and transformed into 67,68Ga-acetylacetonate (67,68Ga(acac)3) before labeling to the DOTA derivatives. The 67Ga or 68Ga labeled complexes were generated by ligand-ligand exchange of acetylacetonate (acac) with the DOTA derivatives. The labeling efficiency of the phenyl-DOTA compound, Ph-DOTA, with 67,68Ga could be higher than 95% under the reaction being facilitated via sonication, at ambient temperature for 20 min. By a similar reaction, the labeling efficiency of 3-NO2-Ph-DOTA with 67,68Ga was found to be lower (~40%). The stability of 67Ga-Ph-DOTA was high, maintaining at ≧ 98% yield even at 24h post-preparation. The 68Ga labeled Ph-DOTA complex was radiochemically characterized to be anionic and hydrophilic. It is anticipated from the result that 68Ga in the form of Ga(III) may be six coordinated with Ph-DOTA by 4N from the ring and 2O from two of the four pendent acetic groups, leaving other two acetic groups uncoordinated. The two free acetic groups on the final 68Ga-labeled ph-DOTA complex may be significant and beneficial for the further conjugation with peptides or antibodies.
67Ga-Ph-DOTA was selected to carry out an animal biodistribution study. The results revealed that the clearance 67Ga-Ph-DOTA from blood was very rapid. Its uptake by brain, heart, muscle and spleen was not considerable and cleared very rapidly. The radioactivity in small intestines was high and increased with time. The results suggested that a considerable fraction secreted via hepatobiliary way. The highly hydrophilic 67Ga-Ph-DOTA was excreted mainly via the kidneys. In conclusion, Ph-DOTA may be further undertaken as a bifunctional chelating agent for conjugating 67,68Ga to the peptide or antibodies.
|
|---|
