Fluorescence resonance energy transfer-based biosensors for monitoring prostate specific antigen

Prostate cancer has become the most commonly diagnosed cancer in men in the United States. Clinical diagnostic procedures currently include prostate-specific antigen (PSA) screening, digital rectal exam, and prostatic needle biopsy. However, these methods lack the sensitivity to detect small lesions that occur in the early stages of cancer and metastasis. I propose a molecular imaging modality that provides a biochemical characterization of localized regions of prostate tissue. Using fluorescence resonance energy transfer (FRET), several peptide substrates have been designed to respond to varying concentrations of PSA with a concomitant increase in fluorescence. In the near-infrared wavelength range, these fluorescent substrates can be imaged through thin sections of tissue to allow surface volume imaging of biochemical function, and thus, to provide additional insight into prostate cancer localization and progression. The goal of this study was to develop novel fluorescent substrates for prostate-specific antigen to serve as indicators of prostate cancer progression. PSA is a biomolecular marker that has gained widespread clinical use in prostate cancer detection. Produced primarily by prostate epithelium, PSA is an androgen-regulated serine protease that acts to cleave semenogelins. Several peptide substrates for PSA have been identified and optimized for specific and efficient hydrolysis. Two of these substrates, QFYSSN and SSIYSQTEEQ were modified with fluorescent dye and quencher molecules to suppress fluorescence in the inactivated form. Light absorbed by the fluorescent molecule is dissipated via nonradiative interaction with the quencher molecule.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Mechanical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Mu, Chunyao Jenny

Advisor dc:contributor.advisor

• Bruce R. Zetter.

• Mechanical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/32360

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/32360