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Junghyun
Kim
Author
Pharmaceutical Sciences Program
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy.
In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials.
Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h).
As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated.
In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
Spring 2017
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
Junghyun
Kim
Author
Pharmaceutical Sciences Program
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy.
In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials.
Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h).
As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated.
In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
Spring 2017
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
Junghyun
Kim
Creator
Pharmaceutical Sciences Program
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC
RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be
over-emphasized. Among several approaches for improving patient outcome and satisfaction,
targeted drug delivery has gained a lot of attention as a solution to maximizing
therapeutic efficacy and minimizing the off-target side effects. Although there have been
tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving
targeted drug delivery, reports on the use of this strategy for delivering therapeutic
radionuclides are scarce. Considering the fact that radiation therapy is a standard of
care for about half of all cancer patients, there is much evidence that more advancements
are needed in the field of targeted delivery of therapeutic radionuclides. In this
dissertation, with the goal of delivering targeted radiation to cancer, a
neutron-activation approach was exploited for producing therapeutic radionuclides with
minimum handling of highly radioactive substances. Various material matrices were explored
for this strategy. In Chapter 1, three different types of radiation therapy – external
beam radiation therapy, internal radiation therapy and systemic radiation therapy – along
with neutron-activatable radionuclides and the rationale for proper isotope selection –
were discussed. Additionally, carbon nanomaterials which have drawn great interest in
numerous research fields for decades were thoroughly reviewed with a focus on biomedical
applications in order to introduce the versatility of these materials. Among carbon-based
matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs)
were chosen and examined for their application to systemic radiation therapy. In Chapter
2, GONs that were designed so that they would not leach neutron-activated radionuclides in
normal tissues but would selectively release their radioactive cargo in the tumor
microenvironment are described. MCNs possessing a more uniform size and shape were
investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To
achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the
pores of MCNs was employed, and this resulted in the MCNs maintaining their structural
integrity with almost no holmium leaching after a prolonged neutron irradiation time (10
h). As an extension of this neutron-activation technology using radioactive needles that
mimicked the microneedle technology adopted in transdermal drug delivery was developed for
internal radiation therapy is described in Chapter 4. The ultimate goal of this work was
to deliver high doses of targeted radiation directly into solid tumors by insertion of the
radioactive needles. As a means to replace current radiation applicators used in the
treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared
as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on
the surface of these needles by pulsed laser deposition and chemical vapor deposition. The
stability of the coatings under physiological-mimicking conditions as well as after
neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and
solid needles containing or coated with neutron-activatable elements were demonstrated to
be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron
flux produced therapeutic amounts of radiation without affecting their physical
integrity.
Spring 2017
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices,
Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron
Activation
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting
institution
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
Junghyun
Kim
Creator
Pharmaceutical Sciences Program
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
Spring 2017
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
Junghyun
Kim
Creator
Division of Pharmacoengineering and Molecular Pharmaceutics
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
Spring 2017
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
Junghyun
Kim
Creator
Division of Pharmacoengineering and Molecular Pharmaceutics
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
2017-05
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
Junghyun
Kim
Creator
Division of Pharmacoengineering and Molecular Pharmaceutics
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
2017-05
Junghyun
Kim
Creator
Division of Pharmacoengineering and Molecular Pharmaceutics
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
2017-05
Junghyun
Kim
Creator
Division of Pharmacoengineering and Molecular Pharmaceutics
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
2017-05
Junghyun
Kim
Creator
Division of Pharmacoengineering and Molecular Pharmaceutics
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation
eng
Doctor of Philosophy
Dissertation
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
2017-05
University of North Carolina at Chapel Hill
Degree granting institution
Junghyun
Kim
Creator
Division of Pharmacoengineering and Molecular Pharmaceutics
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets; Holmium; Material Matrices; Mesoporous Carbon Nanoparticles; Neutron-Activatable Needles; Neutron Activation
eng
Doctor of Philosophy
Dissertation
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
2017-05
University of North Carolina at Chapel Hill
Degree granting institution
Junghyun
Kim
Creator
Division of Pharmacoengineering and Molecular Pharmaceutics
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation
eng
Doctor of Philosophy
Dissertation
University of North Carolina at Chapel Hill Graduate School
Degree granting institution
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
2017-05
Junghyun
Kim
Creator
Division of Pharmacoengineering and Molecular Pharmaceutics
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets, Holmium, Material Matrices, Mesoporous Carbon Nanoparticles, Neutron-Activatable Needles, Neutron Activation
eng
Doctor of Philosophy
Dissertation
Pharmaceutical Sciences
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
2017-05
University of North Carolina at Chapel Hill
Degree granting institution
Junghyun
Kim
Creator
Division of Pharmacoengineering and Molecular Pharmaceutics
Eshelman School of Pharmacy
NEUTRON-ACTIVATION OF MATERIAL MATRICES FOR PRODUCING THERAPEUTIC RADIONUCLIDES
The importance of developing better cancer therapeutics cannot be over-emphasized. Among several approaches for improving patient outcome and satisfaction, targeted drug delivery has gained a lot of attention as a solution to maximizing therapeutic efficacy and minimizing the off-target side effects. Although there have been tremendous improvements in delivering chemotherapeutics using nanocarriers for achieving targeted drug delivery, reports on the use of this strategy for delivering therapeutic radionuclides are scarce. Considering the fact that radiation therapy is a standard of care for about half of all cancer patients, there is much evidence that more advancements are needed in the field of targeted delivery of therapeutic radionuclides. In this dissertation, with the goal of delivering targeted radiation to cancer, a neutron-activation approach was exploited for producing therapeutic radionuclides with minimum handling of highly radioactive substances. Various material matrices were explored for this strategy. In Chapter 1, three different types of radiation therapy – external beam radiation therapy, internal radiation therapy and systemic radiation therapy – along with neutron-activatable radionuclides and the rationale for proper isotope selection – were discussed. Additionally, carbon nanomaterials which have drawn great interest in numerous research fields for decades were thoroughly reviewed with a focus on biomedical applications in order to introduce the versatility of these materials. Among carbon-based matrices, graphene oxide nanoplatelets (GONs) and mesoporous carbon nanoparticles (MCNs) were chosen and examined for their application to systemic radiation therapy. In Chapter 2, GONs that were designed so that they would not leach neutron-activated radionuclides in normal tissues but would selectively release their radioactive cargo in the tumor microenvironment are described. MCNs possessing a more uniform size and shape were investigated as a carrier for the stable isotope 165Ho are presented in Chapter 3. To achieve complete prevention of holmium leaching, the synthesis of holmium oxide in the pores of MCNs was employed, and this resulted in the MCNs maintaining their structural integrity with almost no holmium leaching after a prolonged neutron irradiation time (10 h). As an extension of this neutron-activation technology using radioactive needles that mimicked the microneedle technology adopted in transdermal drug delivery was developed for internal radiation therapy is described in Chapter 4. The ultimate goal of this work was to deliver high doses of targeted radiation directly into solid tumors by insertion of the radioactive needles. As a means to replace current radiation applicators used in the treatment of some solid tumors, custom-sized titanium and molybdenum needles were prepared as base materials. Neutron-activatable radionuclides (holmium and rhenium) were coated on the surface of these needles by pulsed laser deposition and chemical vapor deposition. The stability of the coatings under physiological-mimicking conditions as well as after neutron irradiation was extensively evaluated. In summary, carbon-based nanocarriers and solid needles containing or coated with neutron-activatable elements were demonstrated to be very suitable for use in radiation therapy. Irradiation of these matrices in a neutron flux produced therapeutic amounts of radiation without affecting their physical integrity.
2017
Pharmaceutical sciences
Biomedical engineering
Health sciences
Graphene Oxide Nanoplatelets; Holmium; Material Matrices; Mesoporous Carbon Nanoparticles; Neutron-Activatable Needles; Neutron Activation
eng
Doctor of Philosophy
Dissertation
Michael
Jay
Thesis advisor
Kristy
Ainslie
Thesis advisor
Samuel
Lai
Thesis advisor
Shawn
Hingtgen
Thesis advisor
Matthew
Matthew
Thesis advisor
text
2017-05
University of North Carolina at Chapel Hill
Degree granting institution
Kim_unc_0153D_17147.pdf
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