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Using magnetic resonance imaging and immunohistochemistry to monitor the response of HCT-116 xenograft tumours to tirapazamine Bains, Lauren Jean
Abstract
Tirapazamine is a prodrug which is activated under hypoxic conditions and has shown promise in treating hypoxic tumours. Using MRI and histochemistry, the response of HCT116 xenograft tumours to tirapazamine was investigated and quantified. Dynamic contrast-enhanced and diffusion weighted MRI scans were acquired both before and after treatment with tirapazamine in under two hours of imaging time per session. MRI data was used to produce maps of the apparent diffusion coefficient (ADC), area-under-the-curve (IAUC), and pharmacokinetic parameters (Ktrans, ve, vv). Carbocyanine and BrdU/haematoxylin staining were used to produce histological images of perfusion and necrosis. Implanted fiducial markers were used to align MRI data before and after treatment, and to align MRI slices with histological sections. Qualitative and quantitative comparisons between MRI and histological images showed good agreement between the two. Data from both modalities showed that tirapazamine causes significant changes in diffusion and decreases in perfusion within 24 hours after treatment; widespread vascular shutdown and central necrosis were observed in treated tumours. The agreement of dynamic contrast-enhanced MRI and diffusion weighted MRI with accepted immunohistochemical methods suggests that the MRI techniques presented here are effective methods of monitoring the response of hypoxic, heterogeneous tumours to treatment with tirapazamine. This is the first MR investigation to measure the effects of tirapazamine in an in vivo tumour model. The non-invasive imaging protocol developed here has the potential for direct translation to the clinic in a potential trial. Interestingly, the response of tumours to tirapazamine is evidenced by marked vascular shutdown detected using dynamic contrast enhanced MR imaging, supporting the hypothesis that tirapazamine's mechanism of action may include vascular effects.
Item Metadata
Title |
Using magnetic resonance imaging and immunohistochemistry to monitor the response of HCT-116 xenograft tumours to tirapazamine
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2007
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Description |
Tirapazamine is a prodrug which is activated under hypoxic conditions and
has shown promise in treating hypoxic tumours. Using MRI and histochemistry,
the response of HCT116 xenograft tumours to tirapazamine was investigated
and quantified. Dynamic contrast-enhanced and diffusion weighted
MRI scans were acquired both before and after treatment with tirapazamine
in under two hours of imaging time per session. MRI data was used to produce
maps of the apparent diffusion coefficient (ADC), area-under-the-curve
(IAUC), and pharmacokinetic parameters (Ktrans, ve, vv). Carbocyanine
and BrdU/haematoxylin staining were used to produce histological images
of perfusion and necrosis.
Implanted fiducial markers were used to align MRI data before and after
treatment, and to align MRI slices with histological sections. Qualitative
and quantitative comparisons between MRI and histological images showed
good agreement between the two. Data from both modalities showed that
tirapazamine causes significant changes in diffusion and decreases in perfusion
within 24 hours after treatment; widespread vascular shutdown and
central necrosis were observed in treated tumours. The agreement of dynamic
contrast-enhanced MRI and diffusion weighted MRI with accepted
immunohistochemical methods suggests that the MRI techniques presented
here are effective methods of monitoring the response of hypoxic, heterogeneous
tumours to treatment with tirapazamine.
This is the first MR investigation to measure the effects of tirapazamine
in an in vivo tumour model. The non-invasive imaging protocol developed
here has the potential for direct translation to the clinic in a potential
trial. Interestingly, the response of tumours to tirapazamine is evidenced
by marked vascular shutdown detected using dynamic contrast enhanced
MR imaging, supporting the hypothesis that tirapazamine's mechanism of
action may include vascular effects.
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Genre | |
Type | |
Language |
eng
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Date Available |
2011-02-25
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0084952
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.