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postgraduate thesis: Diethylenetriaminepentaacetic acid (DTPA) based lanthanide (III) complexes for bioimaging application

TitleDiethylenetriaminepentaacetic acid (DTPA) based lanthanide (III) complexes for bioimaging application
Authors
Advisors
Advisor(s):Wong, WT
Issue Date2012
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Ho, K. [何家健]. (2012). Diethylenetriaminepentaacetic acid (DTPA) based lanthanide (III) complexes for bioimaging application. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4979934
AbstractIn this work, a series of DTPA based Ln complexes containing one or two chromophores with different degrees of conjugation were synthesized. The proton relaxivities of Gd(III) analogues were investigated as potential MRI contrast agents while the photoluminescence of Eu(III) and Tb(III) analogues were studied for their applications in optical probes for cellular imaging. Later investigation indicates that only emissions from the chromophores could be measured upon long wavelength photon excitations in the microscope. With suitable ligand design, novel dual functional imaging probes were finally synthesized and these showed good luminescence intensity and image contrast in both in-vivo and in-vitro studies. Eight DTPA based Ln (III) complexes LnL1-L8 containing one or two chromophores which include benzene, 2-aminopyridine, 3-amino-pyridine and 4-aminopyridinewere synthesized. The syntheses, relaxometric properties, hydration numbers, quantum yields, sensitization efficiencies, brightnesses, cytotoxicities and cellular uptake properties were discussed. Those mono-substituted complexes show higher relaxivity, while the di-substituted complexes show lower relaxivity than Gd-DTPA (4.17 mM-1 s-1),a clinically used MRI contrast agent(CA).The di-substituted Tb(III)/Eu(III) analogues show lower sensitization efficiency than the mono-substituted ones in the energy transfer process. Therefore, the experimental results clearly illustrate that the complex with one chromophorein the DTPA system is a better option for being used as a MRI contrast agent and an optical probe. Another eight new mono-substituted DTPA based Ln(III) complexes LnL9-L16 containing extended conjugated chromophores were synthesized and investigated. The phenyl derivatives and naphthyl derivatives were added onto the para-position of 2-aminopyridine that was employed as the chromophore. All GdL9-L16possess one bound water molecule and show higher relaxivity than Gd-DTPA. The relaxivities at 300 MHz at 25oC are in the descending order of GdL15(5.37 mM-1s-1) > GdL16(5.23 mM-1s-1) > GdL13(5.12 mM-1s-1) > GdL14(5.06 mM-1s-1) > GdL11(4.96 mM-1s-1) > GdL12(4.83 mM-1s-1) > GdL10(4.80 mM-1s-1) > GdL9(4.50 mM-1s-1). Their quantum yields, sensitization efficiencies and brightnesses are greatly improved because of the highly conjugated chromophores. Moreover, they all showed low cytotoxicity to cells in a MTT assay and a high accumulation in cells in cellular uptake studies. However, no emission from the Eu(III) ion was detected from the Eu(III) analogues upon long wavelength photon excitation in the cell imaging studies, only the emissions from the chromophores were observed. Two mono-substituted DTPA based Ln(III) complexes containing anthracenyl derivatives as the chromophore LnL17-L18 and two DTPA-based binuclear Ln(III) complexes LnL19-L20were synthesized and investigated. Among the four complexes, GdL18 shows the highest relaxivity (4.65 mM-1s-1) and the highest fluorescent quantum yield (2.45%).It also has low cytotoxicity to cells in MTT assay and high accumulation in cells in cellular uptake study. In addition, GdL18shows very strong binding interaction towards serum albumin, i.e. 318,400mol-1dm3for HSA and 90,200 mol-1dm3for BSA. In preliminary studies, GdL18can both give good luminescence intensity and image contrast in both in vitro cell imaging and in vivo MRI studies. Therefore, GdL18 is considered as a potential candidate for use as a dual functional MRI/optical imaging probe.
DegreeDoctor of Philosophy
SubjectDiethylenetriaminepentaacetic acid.
Lanthanum compounds.
Imaging systems in biology.
Dept/ProgramChemistry
Persistent Identifierhttp://hdl.handle.net/10722/181501

 

DC FieldValueLanguage
dc.contributor.advisorWong, WT-
dc.contributor.authorHo, Ka-kin.-
dc.contributor.author何家健.-
dc.date.accessioned2013-03-03T03:20:17Z-
dc.date.available2013-03-03T03:20:17Z-
dc.date.issued2012-
dc.identifier.citationHo, K. [何家健]. (2012). Diethylenetriaminepentaacetic acid (DTPA) based lanthanide (III) complexes for bioimaging application. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4979934-
dc.identifier.urihttp://hdl.handle.net/10722/181501-
dc.description.abstractIn this work, a series of DTPA based Ln complexes containing one or two chromophores with different degrees of conjugation were synthesized. The proton relaxivities of Gd(III) analogues were investigated as potential MRI contrast agents while the photoluminescence of Eu(III) and Tb(III) analogues were studied for their applications in optical probes for cellular imaging. Later investigation indicates that only emissions from the chromophores could be measured upon long wavelength photon excitations in the microscope. With suitable ligand design, novel dual functional imaging probes were finally synthesized and these showed good luminescence intensity and image contrast in both in-vivo and in-vitro studies. Eight DTPA based Ln (III) complexes LnL1-L8 containing one or two chromophores which include benzene, 2-aminopyridine, 3-amino-pyridine and 4-aminopyridinewere synthesized. The syntheses, relaxometric properties, hydration numbers, quantum yields, sensitization efficiencies, brightnesses, cytotoxicities and cellular uptake properties were discussed. Those mono-substituted complexes show higher relaxivity, while the di-substituted complexes show lower relaxivity than Gd-DTPA (4.17 mM-1 s-1),a clinically used MRI contrast agent(CA).The di-substituted Tb(III)/Eu(III) analogues show lower sensitization efficiency than the mono-substituted ones in the energy transfer process. Therefore, the experimental results clearly illustrate that the complex with one chromophorein the DTPA system is a better option for being used as a MRI contrast agent and an optical probe. Another eight new mono-substituted DTPA based Ln(III) complexes LnL9-L16 containing extended conjugated chromophores were synthesized and investigated. The phenyl derivatives and naphthyl derivatives were added onto the para-position of 2-aminopyridine that was employed as the chromophore. All GdL9-L16possess one bound water molecule and show higher relaxivity than Gd-DTPA. The relaxivities at 300 MHz at 25oC are in the descending order of GdL15(5.37 mM-1s-1) > GdL16(5.23 mM-1s-1) > GdL13(5.12 mM-1s-1) > GdL14(5.06 mM-1s-1) > GdL11(4.96 mM-1s-1) > GdL12(4.83 mM-1s-1) > GdL10(4.80 mM-1s-1) > GdL9(4.50 mM-1s-1). Their quantum yields, sensitization efficiencies and brightnesses are greatly improved because of the highly conjugated chromophores. Moreover, they all showed low cytotoxicity to cells in a MTT assay and a high accumulation in cells in cellular uptake studies. However, no emission from the Eu(III) ion was detected from the Eu(III) analogues upon long wavelength photon excitation in the cell imaging studies, only the emissions from the chromophores were observed. Two mono-substituted DTPA based Ln(III) complexes containing anthracenyl derivatives as the chromophore LnL17-L18 and two DTPA-based binuclear Ln(III) complexes LnL19-L20were synthesized and investigated. Among the four complexes, GdL18 shows the highest relaxivity (4.65 mM-1s-1) and the highest fluorescent quantum yield (2.45%).It also has low cytotoxicity to cells in MTT assay and high accumulation in cells in cellular uptake study. In addition, GdL18shows very strong binding interaction towards serum albumin, i.e. 318,400mol-1dm3for HSA and 90,200 mol-1dm3for BSA. In preliminary studies, GdL18can both give good luminescence intensity and image contrast in both in vitro cell imaging and in vivo MRI studies. Therefore, GdL18 is considered as a potential candidate for use as a dual functional MRI/optical imaging probe.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B49799344-
dc.subject.lcshDiethylenetriaminepentaacetic acid.-
dc.subject.lcshLanthanum compounds.-
dc.subject.lcshImaging systems in biology.-
dc.titleDiethylenetriaminepentaacetic acid (DTPA) based lanthanide (III) complexes for bioimaging application-
dc.typePG_Thesis-
dc.identifier.hkulb4979934-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineChemistry-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4979934-
dc.date.hkucongregation2013-

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