| Summary: | 碩士 === 國立清華大學 === 原子科學系 === 89 === Bifunction chelating agents play an important role in conjugation of radionuclides with peptides and radionuclides. The coupling efficiency with peptides and labeling yield with radionuclides are determined by the choice of bifunctional chelating agents, and further related to the in vivo stability and biodistribution of the eventual radiolebeled conjugates. The main work of this study included synthesis of diaminothiol bifunctional chealting agent─thiolactone, and simulation of binding peptide with thiolactone by using benylamine as a model to assess the feasibility of coupling the bifunctional chelating agent with peptide. Thereafter, the coupling product was labeled by 99mTc to produce 99mTc—thiolactone-benzylamine conjugate. The radiochemical and biological characteristics of the resultant radiolabeled conjugate were examined.
The synthesis of the bifunctional chelating agent─thiolactone proceeded with 9 steps and all the conditions for the first step to the last step were confirmed. The structure of thiolactone and the couple with benzylamine were identified by NMR. Labeling the thioactone─benzylamine couple with 99mTc was carried out by adding 99mTcO4- in the presence of saturated stannous tartrate solution under different pH buffers, where 99mTcO4- was reduced to 99mTcO3+ and simultaneously bound to thiolactone. The labeling efficiency, lipophilicity and stability of 99mTc-thiolactone─benzylamine conjugate were determined by electrophoresis, solvent extraction and thin layer chromatography. Finally, the pharmacological kinetics and biological distribution of the 99mTc labeled conjugate was studied using the mice, C3H/HeN as an animal model.
According to the results, the 99mTc-thioactone─benzylamine conjugate was characterized to be of high labeling yield (~90%), neutrality, high lipophilicity, and good stability. The animal trial revealed that this 99mTc labeled conjugate had a rapid blood clearance rate, and excreted mainly via hepatobiliary metabolism.
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