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shows the differences in the oxygen perfusion. The major blood vessels and muscle bundles separated by
bone were visible. Oxygen gradients from the center of the four major vessels into the distal regions can
be seen in the oxygen map.
The oxygenation status of normal and tumor tissues is an important parameter, being in part responsible
for the effectiveness of cancer therapy. Halpern
et al
.
10
demonstrated the efficiency of low field 250 MHz
EPR oximetry in combination with a mHCTPO probe to report oxygen concentration in the body water
of murine FSa and NFSa fibrosarcomas 7 cm deep in the tissues of a living animal (Figure 16.4). An
oximetric 2-D (1 spectral/1 spatial) spectral image of the tumor was also obtained allowing, in principle,
direct assessment of tumor hypoxia to determine the usefulness of radiation and chemotherapy adjuvants
directed to hypoxic cell compartments. Hydrophobic perdeuterated NR, PDT (Scheme 16.3), has been
applied to measure oxygenation level in lipophilic compartments with higher oxygen solubility in radiation
induced fibrosarcoma (RIF-1) in mice.
82
The data showed a threefold lower level of oxygenation of the
tumor tissue compared with that of the normal muscle.
82
16.4.3 TAM oximetric probes
Nitroxyl radicals were also the first compounds tested in dynamic nuclear polarization (DNP) to probe the
oxygen environment.
83
However, bioreduction of the nitroxides into EPR silent products and comparatively
broad spectral lines complicate their application, particularly for EPR oxygen mapping. In this respect,
triarylmethyl radicals developed for biomedical applications by Nycomed Innovation AB
38
(Scheme 16.2),
have the advantage of extraordinary stability
in vivo
and a very narrow single EPR line of about 100 mG
or less. The oxygen broadening of the TAMs in water is about 500 mG/mM of oxygen
21
similar to that
for the NRs. On the other hand, the concentration broadening of the TAMs is about 10 mG/mM,
21
which
is one order of magnitude less than that for the NRs.
72
These properties make TAM radicals superior
oximetric probes for
in vivo
EPR/EPRI and DNP/PEDRI applications.
21,43
Images of a tumor obtained using 250 MHz EPRI when the mouse was either breathing air or carbo-
gen (95 % oxygen, 5 % carbon dioxide) are shown in Figure 16.6.
84
The images obtained using TAM
Oxo31 probe (Scheme 16.2) show the heterogeneity in the distribution of oxygen in the tumor with
higher [O
2
] values after animal was carbogen-breathing for 10 minutes. Note that continuous wave
spectral - spatial EPRI is based on measurement at numerous magnetic field gradients which typically
requires a long acquisition time, 20 minutes in Figures 16.5 and 16.6, which is often unpractical for
biological use.
Recent developments in PEDRI
85,86
demonstrated that this method allowed simultaneous co-registration
of free radical distribution and anatomic information. Since PEDRI is based on proton MRI, it circumvents
the resolution limitations of EPRI that occur due to very broad line widths of most paramagnetic labels,
and inherently offers high spatial resolution and rapid image data collection. Therefore, PEDRI is now
recognized as a powerful alternative to conventional EPRI. One of the successful applications of functional
PEDRI is oxygen mapping. It is based on the paramagnetic character of dissolved oxygen which affects
the EPR line width of free radical probes and, as a consequence, alters the RF power saturability of
the probes. Therefore, PEDRI with variable saturation power offers a reliable method of imaging oxygen
concentrations
in vivo
using TAM probes.
21,33,43,87
PEDRI oxygen images of a mouse with a tumor obtained
using Oxo63 (Scheme 16.2) are shown in Figure 16.7. Spatially resolved functional information (oxygen
map) was extracted from two PEDRI images collected with interleaving pulse sequences in which the
EPR irradiation was applied at two different power levels, 45 and 3 W. The expanded tumor region clearly
shows heterogeneity in oxygen distribution, severely hypoxic regions, and an increase in the oxygen level
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