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Implantable Depots for Interstitial ...

Lai Dreyer, Priscilla.

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Implantable Depots for Interstitial Delivery of Radiolabeled Gold Nanoparticles Using a Brachytherapy Technique.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Implantable Depots for Interstitial Delivery of Radiolabeled Gold Nanoparticles Using a Brachytherapy Technique./
作者:	Lai Dreyer, Priscilla.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	144 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
Contained By:	Dissertations Abstracts International81-06B.
標題:	Nanotechnology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13857632
ISBN:	9781392477557

Implantable Depots for Interstitial Delivery of Radiolabeled Gold Nanoparticles Using a Brachytherapy Technique.
Lai Dreyer, Priscilla.

Implantable Depots for Interstitial Delivery of Radiolabeled Gold Nanoparticles Using a Brachytherapy Technique. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 144 p.

Source: Dissertations Abstracts International, Volume: 81-06, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2019.

This item must not be sold to any third party vendors.

Radiolabeled gold nanoparticles (AuNP) are emerging as a class of therapeutics for cancer due to their unique physical and chemical properties that differentiate them from other small or bulk materials, as well as other nanoscale particles. In the ideal condition their use as a radiotherapeutic agent is facilitated by preferential extravasation from the tumour vasculature and accumulation in the interstitial space as a result of the enhanced permeability and retention (EPR) effect, following systemic delivery. This delivery scenario was anticipated to reduce the accumulation of radiolabeled AuNP in normal tissues, thereby increasing the therapeutic ratio of tumour control to normal tissue complications. However, systemic delivery of AuNP has been challenged with the inability to escape phagocytic clearance by the reticuloendothelial system (RES) coupled with suboptimal accumulation of AuNP in the tumour. Furthermore, attempts at direct intratumoural delivery of radiolabeled AuNP to circumvent RES capture and increase tumour concentrations have encountered their own limitations such as clinical feasibility and unpredictable intratumoural radioactivity and dose distribution patterns. In contrast brachytherapy, the oldest form of internal radiotherapy, has well established methods to precisely deliver radioactive material. The use of radiolabeled AuNP in brachytherapy can be mutually beneficial, offering new opportunities for brachytherapy such as use of non-photon emitting radionuclides, potential for adjuvant therapies, and dose homogenization from AuNP redistribution in the tumour interstitial space. In this thesis, a delivery system for radiolabeled AuNP is developed by designing an implantable nanoparticle depot (NPD) compatible with traditional permanent brachytherapy techniques. The design of the NPD is validated in its ability to facilitate controlled release of AuNP, resulting in predictable AuNP distributions in breast cancer xenografts in vivo. Furthermore, micro-SPECT/CT (single-photon emission computed tomography/computed tomography) image based dosimetry techniques are applied to estimate the dose distribution surrounding NPD delivery of AuNP labeled with various electron emitting radionuclides. Finally, the efficacy and toxicity of lutetium-177-AuNP NPD is evaluated in two triple negative breast cancer mouse xenograft models. In summary, this thesis outlines the design, associated dosimetry and preclinical application of radiolabeled AuNP using electron emitting radionuclides, delivered by NPD and a permanent brachytherapy technique.

ISBN: 9781392477557Subjects--Topical Terms:

526235
Nanotechnology.
Subjects--Index Terms:

Brachytherapy

Implantable Depots for Interstitial Delivery of Radiolabeled Gold Nanoparticles Using a Brachytherapy Technique.
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520 $a Radiolabeled gold nanoparticles (AuNP) are emerging as a class of therapeutics for cancer due to their unique physical and chemical properties that differentiate them from other small or bulk materials, as well as other nanoscale particles. In the ideal condition their use as a radiotherapeutic agent is facilitated by preferential extravasation from the tumour vasculature and accumulation in the interstitial space as a result of the enhanced permeability and retention (EPR) effect, following systemic delivery. This delivery scenario was anticipated to reduce the accumulation of radiolabeled AuNP in normal tissues, thereby increasing the therapeutic ratio of tumour control to normal tissue complications. However, systemic delivery of AuNP has been challenged with the inability to escape phagocytic clearance by the reticuloendothelial system (RES) coupled with suboptimal accumulation of AuNP in the tumour. Furthermore, attempts at direct intratumoural delivery of radiolabeled AuNP to circumvent RES capture and increase tumour concentrations have encountered their own limitations such as clinical feasibility and unpredictable intratumoural radioactivity and dose distribution patterns. In contrast brachytherapy, the oldest form of internal radiotherapy, has well established methods to precisely deliver radioactive material. The use of radiolabeled AuNP in brachytherapy can be mutually beneficial, offering new opportunities for brachytherapy such as use of non-photon emitting radionuclides, potential for adjuvant therapies, and dose homogenization from AuNP redistribution in the tumour interstitial space. In this thesis, a delivery system for radiolabeled AuNP is developed by designing an implantable nanoparticle depot (NPD) compatible with traditional permanent brachytherapy techniques. The design of the NPD is validated in its ability to facilitate controlled release of AuNP, resulting in predictable AuNP distributions in breast cancer xenografts in vivo. Furthermore, micro-SPECT/CT (single-photon emission computed tomography/computed tomography) image based dosimetry techniques are applied to estimate the dose distribution surrounding NPD delivery of AuNP labeled with various electron emitting radionuclides. Finally, the efficacy and toxicity of lutetium-177-AuNP NPD is evaluated in two triple negative breast cancer mouse xenograft models. In summary, this thesis outlines the design, associated dosimetry and preclinical application of radiolabeled AuNP using electron emitting radionuclides, delivered by NPD and a permanent brachytherapy technique.
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