Lipid-Based Pharmaceutical Nanocarriers for Imaging Applications - Nanotechnology for Biomedical Imaging and Diagnostics - page 56

showed that 99m Tc-labeled nanocarriers accumulated in liver and spleen at 24h
postinjection. The use of 99m Tc-disidA was preferred compared to HmpAo, since
99m Tc-disidA is much cheaper and has a longer shelf life when used for nanocarrier
labeling.
A few years ago, phillips et al . [51] introduced a novel method for radiolabeling
preformed nanocarriers with 99m Tc-N-ethyl-substituted bis(2-mercaptoethyl)amine
and phenylthiolate coligand (s) complexes (sNs/s), which can be applied to nano-
carrier radiolabeling with therapeutic radionuclides, 186 re and 188 re. in his technique,
gsH-loaded nanocarriers were incubated with 99m TC-sNs/s complexes having a
neutral core coordination structure. These 99m TC-sNs/s complexes can change into
hydrophilic complexes following their entry into the inner space of nanocarriers and
reaction with pre-encapsulated gsH, cysteine, or other hydrophilic chemicals con-
taining a thiol group. it was also found that the higher the lipophilicity of the 99m TC-
sNs/s complex, the easier it can pass through the double layer of the nanocarrier
membrane. This method resulted in good labeling efficiency (about 50-70%) and
high in vitro stability of 99m Tc-BmEdA nanocarriers. moreover, these 99m Tc-gsH
nanocarriers also showed the slow blood pool clearance and low spleen accumulation
typical for pEg-coated nanocarriers.
in interpreting and analyzing scintigraphic images with radiolabeled nanocarri-
ers, one has to recognize that these radionuclide labels track the biodistribution of
nanocarriers and do not always track the disposition of encapsulated therapeutic
agents [52]. The particular chelate with which the radionuclide is bound may also
influence the behavior of the radionuclide after the nanocarrier leaves the blood and
becomes metabolized. Thus, ogihara-umeda et al . [53] have shown that when
nanocarrier-encapsulated 67 ga is in the form of 67 ga-nitrilotriacetic acid (NTA)
complex, the 67 ga accumulation in a tumor is twice as high as when 67 ga is used as
67 ga-deferoxamine even at similar blood level of 67 ga-nanocarrier activities at 24 h.
it was speculated that this difference was due to the high affinity of the unbound
67 ga for the tumor tissue, which resulted in 67 ga tumor accumulation after metabo-
lism of the nanocarrier in the region of the tumor and release of 67 ga from the low-
affinity NTA chelate. Hence, the characteristics of the radionuclide and the
radionuclide-ligand complex used in nanocarrier labeling must be always carefully
considered when analyzing the scintigraphic images, particularly after the nanocar-
rier metabolism starts [26].
in a recent comparative analysis, the relative efficacy of entrapment of radiopaque
materials into different nanocarriers and advantages and disadvantages of various
nanocarrier types were reviewed [35]. The maximum entrapment into the inner
nanovesicles interior might be achieved for the vesicles prepared by reverse-phase
evaporation, dehydration/rehydration, and interdigitation/fusion methods. However,
all these methods are difficult to control and scale up. so, from the practical point of
view, the optimum method for nanovesicle loading with contrast material by entrap-
ment is still to be developed.
CT contrast agents (primarily heavily iodinated organic compounds) were included
in the inner water compartment of nanocarriers or incorporated into the nanocarrier
membrane during the nanocarrier preparation [54]. Thus, iopromide-containing