Targeting the receptor for advanced glycation end products with a quantitative multimodal imaging method for precision medicine

Konopka, Christian James

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https://hdl.handle.net/2142/106486 Copy

Description

Title

Targeting the receptor for advanced glycation end products with a quantitative multimodal imaging method for precision medicine

Author(s)

Konopka, Christian James

Issue Date

2019-12-06

Director of Research (if dissertation) or Advisor (if thesis)

Dobrucki, Wawrzyniec L

Doctoral Committee Chair(s)

Dobrucki, Wawrzyniec L

Committee Member(s)

• Smith, Andrew M
• Pan, Dipanjan
• Kajdacsy-Balla, Andre

Department of Study

Bioengineering

Discipline

Bioengineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Molecular Imaging
• Receptor For Advanced Glycation End Products
• Prostate Cancer
• Nanoparticles
• PET-CT

Abstract

The Receptor for Advanced Glycation End Products (RAGE) has been shown to contribute to a myriad of pathologies including nephropathy, Alzheimer’s disease, cardiomyopathy, and pulmonary, ocular, arterial, and atherosclerotic diseases. It has been shown that RAGE expression levels are high during development but markedly decreased in adult tissues; while on the other hand, RAGE expression in adult tissues is significantly augmented by increased levels of ligands named advanced-glycation end-products (AGEs), which are observed in pathological states including inflammation, diabetes, renal and heart failure, and cancer. Yet, the study of RAGE and its ligands in their relation to cancer progression are still in their early stages. Significantly, however, RAGE and its ligands have been shown to be both over expressed and critical to prostate cancer (PCa) development. Importantly, overexpression of RAGE and its ligand HMGB1 clinically has been shown to be associated with poor PCa patient survival, suggesting its promise as a molecular target for imaging and therapeutics. In this work, we developed and employed a nanoparticle-based imaging strategy of RAGE, first in a model of hind-limb ischemia (a widely-studied pathological model for RAGE signaling), and subsequently in PCa. Finally, we demonstrate the utility of this probe and the potential import RAGE and its ligands may play in disease, by using this RAGE-targeted imaging strategy to track the effects of dietary Advanced Glycation End Products on PCa progression. This strategy allows for the development of precision clinical assessment and treatment paradigms, while highlighting the import of this receptor.

Graduation Semester

2019-12

Type of Resource

text

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http://hdl.handle.net/2142/106486

Copyright and License Information

Copyright 2019 Christian J. Konopka

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