Lipid-Based Pharmaceutical Nanocarriers for Imaging Applications - Nanotechnology for Biomedical Imaging and Diagnostics - page 63

already available on the visualization of primary lung cancer, Kaposi sarcoma, and
lymphoma in Aids patients [102] and various other tumors [21, 58]. The use of
99m Tc-dTpA nanocarriers for experimental tumor imaging is also described [103], as
is the use of nanocarriers labeled with 67 ga [104].
pEg-coated, pH-sensitive, and folate-modified liposomes labeled with 159 gd were
used for simultaneous antitumor treatment, biodistribution studies, and scintigraphic
imaging in mice with Ehrlich tumor [105]. pharmacokinetics and dosimetry were
studies using pEgylated liposomes loaded with 111 in-labeled vinorelbin and with
188 re-labeled doxorubicin in two different colon carcinoma models in mice [106].
The imaging was able to prove that both agents have comparable antitumor activity.
interestingly, liposomal contrast agent begin to find their application in veterinary,
and safety and biodistribution study of 99m Tc-labeled liposomes has been performed
in horses [107].
Both animal experiments and clinical studies revealed that in certain cases con-
trast nanocarriers accumulate in tumors indirectly, via loading resident macrophages
[98, 108]. The sensitivity of the method reaches 85%, far exceeding that for tradi-
tional contrast agents.
The use of lipid-coated stable gas-containing microbubbles for sonographic
imaging of experimental brain glyomas in rats is also described earlier [109].
The imaging of lymph nodes plays a major role in the early detection of neoplastic
involvement in cancer patients. Lymph nodes with malignancies contain less normal
macrophage-rich tissue that actively absorbs particulates, and so, on the image (no
matter which imaging modality is used), an abnormal lymph node should have
certain “filling defect” [27]. over 30years ago, conventional nanovesicles were
shown to accumulate in macrophages of regional lymph nodes after subcutaneous
injection. it takes 6-24 h in rat to get the nodes visualized with gamma- or paramag-
netic-labeled nanocarriers [110].
Liposomes modified with already mentioned polychelating polymers (pAp)
loaded with gd together with pEg and tumor-specific antibody demonstrated signif-
icantly enhanced tumor mri with good tumor visualization in mice already after 4 h
(see fig. 3.4) [111].
folate-targeted liposomes loaded with spioN demonstrated strong association
with cancer cells and good signal from these cells in vitro [112]. ferriliposomes
(liposomes loaded with magnetic nanoparticle clusters) have been successfully used
to monitor drug delivery into tumors and tumor microenvironment [113]. similarly,
liposomes coloading with chelated gd and prednisolone phosphate allowed follow-
ing the antitumor activity of the preparation in murine tumor model [114].
more and more often liposomes are used simultaneously bearing contrast moi-
eties for different imaging modalities. Thus, fluorescent paramagnetic liposomes
(calcein + gd chelate) provided multimodal imaging of the cellular uptake of folate-
modified liposomes [115]. Allen's group has described an interesting liposomal
system for simultaneous CT imaging and mri for various image-guided applications
[116]. Another interesting example is multicolor molecular mri using diamagnetic
chemical exchange saturation transfer liposomes [117], which becomes possible
since the diamagnetic saturation transfer contrast is frequency dependent.