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Design & Synthesis Of Enzyme Responsive Contrast Agents Based On Lanthanide For MRI & Optical Imaging

Posted on:2022-12-18Degree:MasterType:Thesis
Country:ChinaCandidate:X C LiFull Text:PDF
GTID:2491306773465404Subject:Biomedicine Engineering
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Cyclen chelates of lanthanide metals are important contrast agents when the 10thsite of cyclen is connected a branched-chain of pyridine animo carbamate,it could be the dual-functional contrast agent for medical nuclear magnetic resonance imaging(MRI)and Optical Imaging(OI),making use of one imaging technology’s advantages combined with those of another imaging technology.The physico-chemical characterization of the model probe Ln(DO3A-NHCbz(6))showed that their distinct luminescence and resonance signals.So we designed a medical molecule based on galactopyanoside of macrocyclic lanthanide,and with the compound we envisaged a retrosynthetic involving the alkylation of a protected DO3A withβ-galactosylated benzyl carbamate of 2-amino-6-bromo-pyridine as shown in the following figure.Because of the chemical reaction properties of galactosylated compounds are relatively complex,only one of three synthetic strategies was realized.We predicted that the designed galactosylated-carbamate DO3A derivative Ln(DO3A-NHCbz Gal(6))was a dual-functional medical imaging agent,which solves the problem of low sensitivity of MRI and low spatial resolution of OI technology.By introducing galactose into modal probe,the derivative can be responsive to galactosidase resulting in activated multifunctional imaging signals.However,since the space linker did not self-immolate and so did not cause signal response,we made discussion at the end of the article and further experimental schemes in the future work.In addition,the synthetic methods of pyridine ring of the 3th,4thor 5thsite of different substitutions of the galactosylated-carbamate DO3A derivatives Ln-complex 3 or 4 or5-NHCOOR(Ln(DO3A-NHCbz Gal(3 or 4 or 5)))were similar to the ways of above.These molecules riched the ligand library for the preparation of lanthanide multifunctional medical imaging agents.
Keywords/Search Tags:molecular imaging, dual-functional contrast agent, MRI, optical imaging, β-galactosidase
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