Catalytic Synthesis and Characterization of Biodegradable ...

Chapter 1
1.6.2.3 Electronic Paramagnetic Resonance (EPR) imaging
Electron paramagnetic resonance imaging (EPRI) is one of the recent functional imaging
modalities that can provide valuable in vivo physiological information, such as tissue redox
status, pO2, pH, and microviscosity, based on variation of EPR spectral characteristics, i.e.,
intensity, linewidth, hyperfine splitting, and spectral shape of free radical probes. 201 EPR
imaging (EPRI) can obtain 1D–3D spatial distribution of such spectral components using
several combinations of magnetic field gradients. With the addition of appropriate
paramagnetic probes, the sensitivity of EPR on a molar basis is about 700 times greater than
that of NMR. For EPRI applications, the spins probes should be (1) chemically stable and
water soluble in biological media; (2) have simple EPR spectrum at ambient temperature; (3)
have pharmacological half-time of at least 10 min to permit the imaging; (4) be
non-toxicity. 202 The most used species are nitroxides, such as TEMPO radicals, due to their
excellent EPR effect. However, the small molecular species pose some limitations, such as
non-selective accumulation in normal tissues, quickly renal clearance, and rapid reduce under
the reduction environment in vivo. 203 To solve these issues, Nagasaki and co-workers have
designed core–shell-type nanoparticles carrying stable radicals in the core (Figure 1.6.8). 204,
205
The nanoparticles showed intense EPR signals and could resist to reduction environment
even at the presence of 3.5 mM ascorbic acid which suggested the promising use of these
nanoparticles to be use as the EPR probes in vivo. Further studies of such nanoparticles
applied in vivo have revealed that the RNPs had more sufficient long-term blood circulation
compared to the TEMPOL free radicals and were of extremely low toxicity due to the
confinement of the TEMPO moieties in the nanoparticle core. Especially, the RNPs were pH
sensitive, the L-band EPR signal could be observed only at the pH value below 6. Therefore,
the pH-sensitive RNPs demonstrated the promising use as the EPR probes for low pH
circumstances in vivo.
Figure 1.6.8 Illustration of the radical-containing nanoparticle. 204
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