lactadherin was labeled by
125 I-iodobenzoyl norbiotinamide [23]. In spite of
advantages of radionuclide imaging of EVs in noninvasive imaging and biodistribution studies, the relative expensiveness of these specialized instruments—SPECT
and PET—limited its wide use for small animal imaging in many research centers.
Furthermore, for clinical translation, compared with magnetic resonance imaging,
radiation hazard should be considered especially with longer half-life radionuclides
with higher energies.
8.1.5 Magnetic Resonance Imaging
Another clinically feasible approach for imaging EVs is labeling with superparamagnetic iron oxide nanoparticles for magnetic resonance imaging [26, 27]. To load
magnetic nanoparticles, a facilitating method for EV loading was required as they
were different from lipophilic dyes which easily passed EV membrane. Hu et al.
employed electroporation of EVs with superparamagnetic iron oxide nanoparticles
to produce nanoparticle-laden EVs [26]. The electroporation for EV loading has
been used for facilitating EV loading of biomaterials such as siRNA [28].
Superparamagnetic iron oxide nanoparticles were labeled to melanoma producing
EVs and they were imaged in vitro and in vivo using magnetic resonance imaging.
However, electric pulse can temporarily disturb the lipid bilayer structure which
may alter the composition of EVs that eventually affect the function. In this regard,
Busato et al. suggested an optimal magnetic nanoparticle labeling method without
electroporation and under physiologic condition [27]. Their strategy was not based
on direct labeling of EVs. Instead, they employed the strategy that parent cells load
ultrasmall superparamagnetic iron oxide nanoparticles.
Magnetic resonance imaging is also clinically applicable and even more, free
from radiation hazard. However, due to limitation in sensitivity and thus they
needed to administer much larger amount of EVs, current in vivo magnetic resonance images were only obtained after intramuscular injection [26, 27]. Though
locally accumulated EVs at injection sites could produce discernable magnetic
resonance signal intensity change, systemic biodistribution and accumulation in
target tissues such as cancer and inflammation require higher sensitivity. Thus,
increasing sensitivity for tracking of systemically administered magnetic
nanoparticle-labeled EVs is required to avoid the necessity to administer too large
amount of EVs to yield sufficient signal-to-noise ratio. The quantitative analysis is
also limited in magnetic resonance imaging compared with radionuclide imaging.
8 Endogenous Radionanomedicine: Biodistribution and Imaging
157
125 I-iodobenzoyl norbiotinamide [23]. In spite of
advantages of radionuclide imaging of EVs in noninvasive imaging and biodistribution studies, the relative expensiveness of these specialized instruments—SPECT
and PET—limited its wide use for small animal imaging in many research centers.
Furthermore, for clinical translation, compared with magnetic resonance imaging,
radiation hazard should be considered especially with longer half-life radionuclides
with higher energies.
8.1.5 Magnetic Resonance Imaging
Another clinically feasible approach for imaging EVs is labeling with superparamagnetic iron oxide nanoparticles for magnetic resonance imaging [26, 27]. To load
magnetic nanoparticles, a facilitating method for EV loading was required as they
were different from lipophilic dyes which easily passed EV membrane. Hu et al.
employed electroporation of EVs with superparamagnetic iron oxide nanoparticles
to produce nanoparticle-laden EVs [26]. The electroporation for EV loading has
been used for facilitating EV loading of biomaterials such as siRNA [28].
Superparamagnetic iron oxide nanoparticles were labeled to melanoma producing
EVs and they were imaged in vitro and in vivo using magnetic resonance imaging.
However, electric pulse can temporarily disturb the lipid bilayer structure which
may alter the composition of EVs that eventually affect the function. In this regard,
Busato et al. suggested an optimal magnetic nanoparticle labeling method without
electroporation and under physiologic condition [27]. Their strategy was not based
on direct labeling of EVs. Instead, they employed the strategy that parent cells load
ultrasmall superparamagnetic iron oxide nanoparticles.
Magnetic resonance imaging is also clinically applicable and even more, free
from radiation hazard. However, due to limitation in sensitivity and thus they
needed to administer much larger amount of EVs, current in vivo magnetic resonance images were only obtained after intramuscular injection [26, 27]. Though
locally accumulated EVs at injection sites could produce discernable magnetic
resonance signal intensity change, systemic biodistribution and accumulation in
target tissues such as cancer and inflammation require higher sensitivity. Thus,
increasing sensitivity for tracking of systemically administered magnetic
nanoparticle-labeled EVs is required to avoid the necessity to administer too large
amount of EVs to yield sufficient signal-to-noise ratio. The quantitative analysis is
also limited in magnetic resonance imaging compared with radionuclide imaging.
8 Endogenous Radionanomedicine: Biodistribution and Imaging
157