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10 Radiation Therapy Chapter 3

10 Radiation Therapy Chapter 3

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Categories:Types, Research, Science
Published by: samster on May 13, 2009
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02/01/2013

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 RADIATION THERAPY 50
Chapter 3
Murine Tumor
19
F Experiments
The following experiment was started by Dr. Bernard Dardzinski during his stay at WPIas a Ph.D. student. Not only was Dr. Dardzinski responsible for much of the pioneeringwork leading up to this experiment, but he was also integrally involved in the design andexecution of this particular experiment. One of the problems encountered during thecourse of this experiment was in the data analysis stage. Since both spectroscopic andimaging data were collected for the murine tumor oxygenation measurements, weexpected that the information obtained from both methods would be comparable. Mycontribution to this project was in the analysis of the data and reconciling the differencesbetween the spectroscopic and imaging data. Dr. Dardzinski was responsible for theacquisition of the data. While Dr. Dardzinski started the writing, I was responsible foranalyzing the data and completing the writing of this manuscript.
 
 RADIATION THERAPY 51
3.1. Radiation Therapy
3.1.1. Abstract
Radiotherapy studies in mice using perfluoro-15-crown-5-ether showed a decrease in
 p
O
2
 following a single large dose of radiation. In conjunction with spectroscopic data,Inversion-Recovery Echo-Planar-Imaging data were collected at 1-3 hours, 10-13 hours,and 19-26 hours post irradiation, and
1
-maps generated in order to display localizedchanges in
 p
O
2
. The calculated
1
-maps were then weighted by their respective M
0
-mapsto find the weighted average of the
1
-maps, and an equivalent
 p
O
2
of the tumor was thencalculated from the weighted average. Untreated control animals that were subjected tothe same time course showed no evidence of 
 p
O
2
decline, while the tumors irradiatedwith a single dose of 6 MeV electrons showed a decline in
 p
O
2
by approximately 9 torralmost immediately after irradiation. The calculation of 
 p
O
2
using the weighted averageof the
1
-maps was not only highly correlated to the spectroscopic measurements, it wasapproximately equivalent to the spectroscopic measurements. It is speculated that thedecrease in the tissue oxygenation following radiation therapy is due to vascular damagecaused by such a high dose of radiation, or edema within the interstitium of the tumor.Edema can cause the interstitial pressure to increase, resulting in vascular collapse. Thisin turn would lead to decreased perfusion and thus decreased oxygen delivery.
 
 
 RADIATION THERAPY 52
3.1.2. Introduction
Fluorine-19 MRI of exogenously administered PFC emulsions have seen wide-spread usein biomedical applications, especially since their introduction as artificial bloodsubstitutes. By administering these agents intravascularly,
19
F MRI can provideanatomical or physiological information wherever these compounds perfuse or aresequestered. Imaging of the vascular system has been performed in large blood vessels inthe heart and brain
 
(Joseph, 1985a; Joseph
et al
., 1985b; Eidelberg
et al
., 1988a;Eidelberg
et al
., 1988b) and imaging of murine tumor vascularity to assess heterogeneity,necrosis, and the effects of photodynamic therapy has been demonstrated
 
(Ceckler
et al
.,1990).
19
F MRI has also been used to image fluorine in lungs of mice submersed inoxygen-enriched PFCs
 
(Thomas
et al
., 1986). Since PFC emulsions are foreignsubstances in the body of the host, large amounts of PFCs are sequestered in thereticuloendothelial system (RES) of the liver and spleen. This sequestration has made
19
FMRI amenable to studying the biodistribution of PFCs in these organs
 
(McFarland
et al
.,1985; Ratner
et al
., 1987a; Sotak 
et al
., 1993a; Sotak 
et al
., 1993b; Barker
et al
., 1993;Dardzinski
et al
., 1993a). Macrophage activity present in tumors and abscesses hasallowed the use of 
19
F MRI to image PFCs sequestered in these lesions (Sotak 
et al
.,1993b; Longmaid
et al
., 1985; Ratner
et al
., 1988; Sotak 
et al
., 1991; Dardzinski
et al
.,1993b; Dardzinski
et al
., 1993c).

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