ERA

Download the full-sized PDF of Synthesis and Characterization of Novel Radiolabelled Substrates for Imaging of GLUT5 Expression in Human Breast Cancer Using Positron Emission TomographyDownload the full-sized PDF

Analytics

Share

Permanent link (DOI): https://doi.org/10.7939/R3SN01F75

Download

Export to: EndNote  |  Zotero  |  Mendeley

Communities

This file is in the following communities:

Graduate Studies and Research, Faculty of

Collections

This file is in the following collections:

Theses and Dissertations

Synthesis and Characterization of Novel Radiolabelled Substrates for Imaging of GLUT5 Expression in Human Breast Cancer Using Positron Emission Tomography Open Access

Descriptions

Other title
Subject/Keyword
Fructose
Breast Cancer
Positron Emission Tomography
GLUTs
Hexose Transport
Cancer
GLUT5
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Trayner, Brendan J
Supervisor and department
Cheeseman, Chris I (Physiology)
Examining committee member and department
Luyt, Len (External - Oncology/Chemistry, University of Western Ontario)
Murray, David (Oncology)
Mercer, John (Oncology)
McEwan, Sandy (Oncology)
Department
Department of Physiology
Specialization

Date accepted
2012-09-25T15:48:16Z
Graduation date
2012-09
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Overactive glucose transport and metabolism has been widely recognized as one of the fundamental hallmarks of cancer and its progression. The facilitative glucose transporter GLUT1 is widely overexpressed in many tumor types compared to their untransformed counterparts. Due to this, the glucose analogue, 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has been used widely for the imaging of malignant neoplastic tissue through a non-invasive technique, positron emission tomography (PET). PET scans have been very successful in the imaging of many breast cancers expressing high levels of GLUT1, but unfortunately, many breast tumors do not express GLUT1 at high levels, if at all. Clinically, this lack of GLUT1 expression in tumors has led to false-negatives in patients’ PET scans. Interestingly, in 1996 it was first identified that the fructose transporting facilitative hexose transporter GLUT5 is highly expressed in transformed breast tissue compared to the untransformed surrounding tissue. This finding has led to the suggestion that radiolabeled substrates for GLUT5 may be effective in imaging GLUT1 negative, GLUT5 positive tumors. We have rationally designed and synthesized several compounds based around previously performed structural studies and analyzed their behaviour both in vitro and in vivo. The C-6 labelled fructose analogue 6-deoxy-6-[18F]fluoro-D-fructose (6-FDF) has shown favourable in vitro and in vivo characteristics for the imaging of GLUT5 expressing breast tumors. Additionally, its dosimetry and excretory profile suggest the viability of the compound for a clinical trial. Other substrates based on the C2 symmetric fructose mimic 2,5-anhydro-D-mannitol (2,5-AM) have also been examined for their behaviour in vitro and in vivo. Further work will be spent on further characterizing additional fructose and 2,5-AM analogues that will shed more light on the structural requirements of GLUT5 and perhaps lead to other tracers that will show utility in the imaging of GLUT5 expressing breast cancer with PET.
Language
English
DOI
doi:10.7939/R3SN01F75
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication

File Details

Date Uploaded
Date Modified
2014-04-29T18:01:57.816+00:00
Audit Status
Audits have not yet been run on this file.
Characterization
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 6012025
Last modified: 2015:10:12 19:13:37-06:00
Filename: THESIS FINAL.pdf
Original checksum: 6e45e9b66968cd4254c2e1e3e3f15f02
Well formed: true
Valid: true
Status message: Too many fonts to report; some fonts omitted. Total fonts = 1627
File author: B-Tray
Page count: 321
File language: en-CA
Activity of users you follow
User Activity Date