Non-invasive dynamic optical imaging of small animals requires the
development of a novel fluorescence imaging modality. Herein, fluorescence imaging is
demonstrated with sub-second camera integration times using agents specifically
targeted to disease markers, enabling rapid detection of cancerous regions. The
continuous-wave fluorescence imaging acquires data with an intensified or an electronmultiplying
charge-coupled device. The work presented in this dissertation (i) assessed
dose-dependent uptake using dynamic fluorescence imaging and pharmacokinetic (PK)
models, (ii) evaluated disease marker availability in two different xenograft tumors, (iii)
compared the impact of autofluorescence in fluorescence imaging of near-infrared (NIR)
vs. red light excitable fluorescent contrast agents, (iv) demonstrated dual-wavelength
fluorescence imaging of angiogenic vessels and lymphatics associated with a xenograft
tumor model, and (v) examined dynamic multi-wavelength, whole-body fluorescence
imaging with two different fluorescent contrast agents.
PK analysis showed that the uptake of Cy5.5-c(KRGDf) in xenograft tumor
regions linearly increased with doses of Cy5.5-c(KRGDf) up to 1.5 nmol/mouse. Above 1.5 nmol/mouse, the uptake did not increase with doses, suggesting receptor saturation.
Target to background ratio (TBR) and PK analysis for two different tumor cell lines
showed that while Kaposi’s sarcoma (KS1767) exhibited early and rapid uptake of
Cy5.5-c(KRGDf), human melanoma tumors (M21) had non-significant TBR differences
and early uptake rates similar to the contralateral normal tissue regions. The differences
may be due to different compartment location of the target.
A comparison of fluorescence imaging with NIR vs. red light excitable
fluorescent dyes demonstrates that NIR dyes are associated with less background signal,
enabling rapid tumor detection. In contrast, animals injected with red light excitable
fluorescent dyes showed high autofluorescence.
Dual-wavelength fluorescence images were acquired using a targeted 111In-
DTPA-K(IRDye800)-c(KRGDf) to selectively detect tumor angiogenesis and an
untargeted Cy5.5 to image lymphatics. After acquiring the experimental data,
fluorescence image-guided surgery was performed.
Dynamic, multi-wavelength fluorescence imaging was accomplished using a
liquid crystal tunable filter (LCTF). Excitation light was used for reflectance images
with a LCTF transmitting a shorter wavelength than the peak in the excitation light
spectrum. Therefore, images can be dynamically acquired alternating frame by frame
between emission and excitation light, which should enable image-guided surgery.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-1064 |
| Date | 15 May 2009 |
| Creators | Kwon, Sun Kuk |
| Contributors | Sevick-Muraca, Eva M. |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | electronic, application/pdf, born digital |
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