Radio-labeled Nanoparticles for Biomedical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 202

disrupting, which makes them a candidate for cytoplasmic delivery and imaging
[125, 126]. With an acid-degradable cross-linker, the entrapped payload can be
released in a pH-dependent manner inside endosomes [127]. for better cellular
delivery, a cell-penetrating peptide (Cpp) can be used on the nanoparticles to get var-
ious cargos into the cells without disturbing the stability of the cell membrane and
with low cytotoxic effects [128]. In a recent study, it was reported that the optimal
size for deposition in the deep lung for systemic delivery is approximately 1-3 µm—
microparticles rather than nanoparticles [129]. Therefore, a nona-arginine-function-
alized polyacrylamide-based microparticle was synthesized to study the delivery
efficiency of entrapped protein into nonphagocytic lung epithelial cells (beAS-2b).
In vitro results showed effective delivery of encapsulated bSA-Alexa fluor 488 into
the beAS-2b cells in both Cpp- and concentration-dependent manners, as well as a
time dependency [130]. This Cpp-modified microparticle was then labeled with
radiohalogens ( 125 I and 76 br) for animal studies to assess the in vivo fate, lung reten-
tion, and cellular uptake after intratracheal administration. furthermore, nanosized
Cpp particles were synthesized to compare size-related differences in clearance pro-
files. biodistribution studies revealed that particle retention and extrapulmonary dis-
tribution were, in part, size dependent. microparticles were rapidly cleared by
mucociliary routes but, unexpectedly, also through circulation. In contrast, nanopar-
ticles had prolonged lung retention enhanced by the Cpp, which was confirmed with
peT imaging analysis using 76 br-radiolabeled nanoparticles (fig. 7.3). These studies
indicate the potential of microparticles for short-term applications as well as the ben-
efits of nanoparticles for serial imaging or therapy of a persistent lung injury [131].
In contrast, a study of acute lung injury used latex nanoparticles coated with anti-
intercellular adhesion molecule-1(ICAm-1) antibody and labeled with 64 Cu for tar-
geting the pulmonary endothelium. biodistribution studies showed three- to four-fold
higher uptake in the lungs of mice injected with ICAm-targeted nanoparticles than
those receiving control nanoparticles. peT imaging demonstrated the accumulation
of radioactivity in the lungs. However, metabolic studies showed that the in vivo sta-
bility of this nanoprobe needs further improvement for prolonged pulmonary drug
delivery [132].

7.4.5 Radiolabeled carbon-based Nanostructures for pet imaging

CNTs have also been radiolabeled with peT isotopes either on the surface or by
encapsulation within their inner walls. The use of radiolabeled 89 Zr-CNTs for peT
oncological imaging has gained interest due to the unique decay properties of 89 Zr
( t 1/2 = 78.4 h) as well as the availability of high specific activity product [133]. In an
LS174T colon carcinoma model, 89 Zr-labeled SWCNT-([ 89 Zr]-DfO) showed rapid
tumor accumulation and gradually increasing tumor-to-muscle contrast ratio over
time (1.61 at 1 h to 5.08 at 96 h p.i.). In another colon carcinoma model (CT26), a
89 Zr-labeled cross-linked dextran nanoparticle showed primary localization in the
lymph node (34 ± 16% ID/g). In tumor-bearing mice, peT imaging showed intense
tumor uptake (20 ± 5% ID/g), surprisingly higher than other ReS organs, indicating
translational potential [134]. A new type of promising carbon biomaterial known