Lipid-Based Pharmaceutical Nanocarriers for Imaging Applications - Nanotechnology for Biomedical Imaging and Diagnostics - page 52

(a)

(b)

Phospholipids
Cholesterol

Radionuclide
heavy metal

Amphiphilic
unimer

DTPA-chelator

Lipid anchor

figure 3.1 schematics of radionuclide or mr contrast metal association with liposomes
or micelles via the amphiphilic chelate.

in the case of mri imaging agents, to achieve a better mr signal, all reporter
metal atoms should be freely exposed for interaction with water. This requirement
makes metal encapsulation into the nanocarrier less attractive than metal coupling
with polymeric chelators exposed into the outer water space. Nanocarriers loaded
with chelated paramagnetic ions (gd, dy, mn, fe) have been demonstrated to be
useful as mri contrast agents mostly for the visualization of the macrophage-rich
tissues such as rEs organs [35].
The low-molecular-weight water-soluble paramagnetic probes may leak from
nanocarriers upon contact with body fluids, which destabilizes most liposomal
membranes. moreover, it has been shown that when too high concentrations of
gd-dTpA are encapsulated inside nanocarriers for the better enhancement, the
relaxivity of the compound might be even lower than for nonencapsulated gd-dTpA
complex, probably because of decreased residence lifetime of water molecules
inside vesicles [36]. membranotropic chelating agents—dTpA-sA [37] and
dTpA-pE [38]—consist of the polar head containing chelated paramagnetic atom
and the lipid moiety, which anchors the metal-chelate complex in the nanocarrier
membrane. This approach has been shown to be far more superior in terms of the
relaxivity of the final preparation when compared with nanocarrier-encapsulated
paramagnetic ions due to the decrease in the rotational correlation times of the para-
magnetic moiety rigidly connected with relatively large particle [36]. Nanocarriers
with membrane-bound paramagnetic ion demonstrate also the reduced risk of the
leakage in the body. membranotropic chelates are suitable for micelle incorporation
(they anchor in the hydrophobic micelle core) and may also serve to load liposomes
and micelles with heavy radiometals (see fig. 3.1).
A second method has been recently developed by Laverman et al . [39]. With this
method, the highly stable 99m Tc chelator, hydrazino nicotinamide (HYNiC), is