Photodynamic therapy (PDT) has been considered a favorable approach in
certain oncology applications for its little invasiveness and better targeting
specificity compared to conventional therapies. In PDT, localized photosensitizers
can be activated by light to produce cytotoxic oxygen species. However, the
prescribed drug and light doses do not provide satisfying outcomes as the PDT
efficacy relies strongly on the interplay between localized dose factors. Therefore,
the fluorescence emission from active photosensitizers has been investigated
extensively for real-time PDT dosimetry.
This dissertation focuses on characterizing fluorescence properties of two
photosensitizers, Photofrin® and PpIX, in cellular models and discusses about their
potential clinical applications. First, we introduc time-resolve fluorescence (TRF)
of photosensitizers as a potential tool in PDT dosimetry. TRF acquires fluorescence
decay profiles and it is sensitive to drug-microenvironment interactions that occur
frequently in PDT. Therefore, it provides complementary information in addition to
fluorescence spectra that could be subject to intensity artifacts. In this dissertation,
we review TRF studies on PDT photosensitizers, and quantify TRF parameters of
Photofrin® at various subcellular locations. Moreover, analytical solutions are
developed to correct distorted TRF measurements from commonly used
time-domain data acquisition.
Second, we report a new concept – integrated detection and treatment of
Barrett’s Esophagus (BE). BE is a pre-cancerous lesion considered as a major risk
factor in developing esophageal cancers. However, early intervention of BE has
remained a challenging issue as tissue biopsy introduces significant sampling errors
and the separate procedures between diagnosis and treatment add relocation errors.
We proposed to use PpIX fluorescence to highlight morphological features at the
cellular level for quantitative classification, followed by well-characterized
treatment. Current proof-of-concept studies were performed separately, whilst the
detection and treatment can be integrated using confocal endomicroscopy
technology. Overall, these studies examine the potential benefits provided by
fluorescence of photosensitizers for cancer diagnosis and treatment monitoring. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/16735 |
| Date | 06 February 2015 |
| Creators | Yeh, Shu-Chi |
| Contributors | Fang, Qiyin, Biomedical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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