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A NOVEL DESIGN OF INTEGRIN α2β1 TARGETING PEPTIDE PROBE FOR MOLECULAR IMAGING IN PROSTATE CANCER
by
Chiun-Wei Huang
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(BIOMEDICAL ENGINEERING)
May 2011
Copyright 2011 Chiun-Wei Huang
Object Description
| Title | A novel design of integrin α2β1 targeting peptide probe for molecular imaging in prostate cancer |
| Author | Huang, Chiun-Wei |
| Author email | chiunweh@usc.edu; steincafe77@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biomedical Engineering |
| School | Viterbi School of Engineering |
| Date defended/completed | 2010-12-20 |
| Date submitted | 2011 |
| Restricted until | Unrestricted |
| Date published | 2011-01-11 |
| Advisor (committee chair) | Conti, Peter S. |
| Advisor (committee member) |
Shung, Kirk K. Jadvar, Hossein Neamati, Nouri Mackay, J. Andrew |
| Abstract | Prostate cancer is one of the leading causes of cancer-related deaths in the United States and Europe. Despite the fact that prostate-specific antigen (PSA) screening has greatly increased the number of patients with early stage prostate cancer who can be cured by radical prostatectomy, about 40% of prostate cancers are first detected at an advanced stage and half of these are found to be extracapsular at pathologic staging. Therefore, development of an accurate noninvasive imaging technique to detect primary, recurrent and residual prostate cancer is critical for the effective management of this group of patients.; Accumulating experimental evidence indicates that integrins presented on various tumor types are differentially expressed during tumor transformation, progression, and metastasis. Development of integrin cell expression profiles of individual tumors may have further potential in identifying a cell surface signature for a specific tumor type and/or stage. Multiple lines of literature studies indicated that the upregulation or overexpression of α2β1 integrin may correlate with tumor progression in human prostate cancer. For example, the more aggressive PC-3 cell line has the highest expression of α2β1 integrin compared with other less aggressive cell lines, such as CWR-22 (medium expression of α2β1) and LNCap (low expression of α2β1). Noninvasive imaging of this receptor with radiolabeled peptides that specifically target α2β1 integrin could therefore be useful to decipher the invasive potential of prostate cancers.; High sensitivity positron emission tomography coupled with computed tomography for anatomical evaluation, PET/CT, has become a critical diagnostic imaging tool in the identification of a diverse group of malignancies. In this study, we use the knowledge of chemistry, radiochemistry, biochemistry, biology and molecular imaging to develop clinically translatable α2β1 integrin targeting PET probes for prostate cancer imaging. A series of α2β1 integrin targeting peptides were synthesized and their specificity was verified both in vitro and in vivo at the molecular level in preclinical prostate tumor models. The success of the proposed study may provide a better understanding of basic biological mechanisms of prostate cancer, help us more appropriately select patients considered for anti-integrin α2β1 treatment, and allow the evaluation of disease course and therapeutic efficacy at the earliest stages of treatment. |
| Keyword | prostate cancer; integrin α2β1; PET; molecular imaging |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3610 |
| Contributing entity | University of Southern California |
| Rights | Huang, Chiun-Wei |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@dots.usc.edu |
| Filename | etd-HUANG-4270 |
| Archival file | uscthesesreloadpub_Volume17/etd-HUANG-4270.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | A NOVEL DESIGN OF INTEGRIN α2β1 TARGETING PEPTIDE PROBE FOR MOLECULAR IMAGING IN PROSTATE CANCER by Chiun-Wei Huang A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (BIOMEDICAL ENGINEERING) May 2011 Copyright 2011 Chiun-Wei Huang |
