Lipid-Based Pharmaceutical Nanocarriers for Imaging Applications - Nanotechnology for Biomedical Imaging and Diagnostics - page 51

to produce 99m Tc-labeled nanocarriers that were not stable when injected in vivo , with
frequent dissociation of the 99m Tc from the nanocarrier after administration [27].

3.2.3 Label incorporation into the Lipid Bilayer of preformed Nanocarriers

preformed nanocarriers can be also labeled by incubation with a lipophilic chelator
into which the radioisotope has been chelated, prior to the incubation with the lipid
suspension. Although this method provides high labeling efficiency, its in vivo sta-
bility was questionable, because most of these lipophilic labels can readily exchange
with lipoprotein components in blood [28].
morgan et al . [29] were among the first to label liposomes and micelles (mLVs)
with 99m Tc by reducing pertechnetate with tin (stannous) chloride in the presence of
the nanovesicle. in animal studies, the liposomal preparation labeled according to
this “stannous chloride method” showed relatively high uptake of the radiolabel
in kidneys and bladder, suggesting extensive in vivo release of the radiolabel from
liposomes. This in fact was confirmed by other groups [30, 31]. several methods to
label nanocarriers with 99m Tc have been developed. Alafandy et al . developed the
oxidoreduction method [32], as an improved version of the stannous chloride method.
Nanocarriers were prepared with tin(ii) dioxinate complexes inserted in the bilayers.
However, this method required a series of extensive washing in order to remove the
free pertechnetate from the nanocarriers [33].

3.2.4 surface Labeling of preformed Nanocarrier by incorporating
the Lipid-chelator conjugate during preparation

Another approach is to incorporate a lipid chelator into the vesicles during the for-
mulation stage, particularly during the preparation of the lipid film [20]. These
amphiphilic chelators are composed of diethylene triamine pentaacetic acid (dTpA)
conjugated to the head group region of a long-chain fatty acid or phospholipid
molecule. The chelator is incorporated into the lipid components of the bilayer
prior to the actual preparation of the nanocarriers. After hydration of the phospho-
lipids, the chelator is exposed on the outer surface of the nanocarriers, thus being
easily accessible for the radionuclide. The nanocarriers are then incubated with the
radioisotope, which becomes bound to the chelator present on the external surface
of the nanocarrier. still, lipid-chelator systems described to date suffer from
decreased in vivo stability, mainly due to the exposure of the radiolabel on the
surface of nanocarrier [33].
Historically, Hnatowich et al . described the synthesis of a long hydrocarbon chain
covalently coupled to dTpA [22]. These nanocarriers could be labeled with 67 ga or
99m Tc. However, labeling efficiencies did not exceed 60%. during the incubation in
50% human serum, approximately 30% of the 99m Tc activity was released from the
nanocarriers, indicating the instability of these radiolabeled formulations. Later,
goto et al . developed nanocarriers containing stearylamine (sA)-dTpA conjugates
to label nanocarriers with 99m Tc [34]. These preparations showed good in vitro
stability in 50% human serum.