<p> Photodynamic therapy (PDn is an effective treatment option for various
types of invasive tumors, the efficacy of which depends strongly on selective cell
uptake and selective excitation of the tumor, which relies on proper dosage. The
characterization of the fluorescence lifetimes of photosensitizers localized inside
living cells may provide the basis for further investigation of in vitro PDT dosage
measurements using time-domain spectroscopy and imaging. In this thesis, the
fluorescence lifetimes of localized Photofrin ® and delta-aminolevulinic acid
(ALA) induced protoporphyrin IX (PpiX) were investigated in living MAT-LyLu
(MLL) rat prostate adenocarcinoma cells. Cells were incubated with the
photosensitizers, and then treated with light under well-oxygenated conditions
using a two-photon fluorescence lifetime imaging microscope (FLIM).
Fluorescence lifetime images of these cells were recorded with average lifetimes
of 5.5 ± 1.2 ns for Photofrin and 6.3 ± 1.2 ns for ALA-induced PpiX over 600 to
750 nm. Two channel FLIM revealed lifetimes of7.8 ± 0.5 ns for Photofrin® and
10.8 ± 1.7 ns for PpiX over 620 to 645 nm, while photoproducts observed on the
second channel yielded lifetimes of 5.1 ± 0.4 ns over 650 to 670 nm for
Photofrin® and 6.3 ± 1.0 ns over 670 to 690 nm for PpiX. Fluorescence lifetimes
of both photosensitizers were found to be significantly shorter when localized in
cells than when measured in solutions, suggesting that photosensitizers' lifetimes
go through significant changes when bonded to intracellular components. These
changes in lifetime also provide opportunities to quantitatively measure and
monitor the binding states of the photosensitizers and their microenvironment, which may be used in real-time PDT dosimetry, as well as for diagnostic
purposes. </p> / Thesis / Master of Applied Science (MASc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22468 |
| Date | 04 1900 |
| Creators | Russell, Jennifer |
| Contributors | Fang, Qiyin, Hayward, Joseph, Biomedical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
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