Radio-labeled Nanoparticles for Biomedical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 200

accumulation in the liver and intestine. peT/CT imaging showed significant locali-
zation of 64 Cu-TNp in the thoracic aorta with a target-to-background ratio of 5.1 ± 0.9,
indicating potential for clinical translatability. In a similar study, an 18 f-radiolabeled
iron oxide nanoparticle ( 18 f-CLIO) was developed due to the wide availability,
sensitivity, and covalent radiolabeling of this radioisotope [19]. With rapid 18 f
click fluorination, high radiolabeling efficiency and specific activity were achieved
(6.8 ± 0.8 × 10 8 bq/mg fe of nanoparticle). In vivo pharmacokinetic studies showed
comparable blood retention to 64 Cu-TNp. In an apoe −/− aneurysm mouse model, peT
images showed that the avid internalization by phagocytic cells led to significantly
higher tracer accumulation at aneurysms relative to wild-type aorta [99].
peg-coated iron oxide nanoparticles have also been radiolabeled with 64 Cu via
a DOTA functionality (specific activity = 3.7 - 7.4 × 10 8 bq/mg fe). High blood
retention of 37.3 ± 12.9% ID/g at 1 h p.i. in mice was observed as confirmed by peT
imaging [96]. In another study, a cyclic RgD peptide (c(RgDfC)) was conjugated
to a SpIO for targeted peT/mR tumor imaging [100, 101]. This 64 Cu-cRgD-SpION
gave low (<15% ID/g) hepatic burden up to 48 h p.i. and constant tumor uptake
(~5% ID/g) across the study timeline, with the highest tumor-to-muscle ratio
(11.3 ± 2.5) observed at 48 h p.i. Compared to the control 64 Cu-SpIO, 64 Cu-cRgD-
SpIO had significantly ( p < 0.05) higher tumor accumulation during the study, indi-
cating α v β 3 -specific targeting [98].

7.4.4 Radiolabeled polymeric Nanoparticles for pet imaging

Among various nanostructures such as iron oxide, silica, and AuNps [102-106],
amphiphilic core-shell nanostructures have received particular attention because of
their tunable in vivo pharmacokinetics and versatile conjugation chemistry [107, 108].
Shell cross-linked knedel-like nanoparticles (SCK-Nps) are comprised of a hydro-
phobic polystyrene core that can be used to load hydrophobic drug molecules and a
hydrophilic external shell of poly(acrylic acid-co-acrylamide) that provides additional
sites for functional units such as imaging moieties. Through various synthetic strat-
egies, especially cross-linking, SCK-Nps can be prepared with controlled size, surface
charge, pegylation density, functionality, and in vivo pharmacokinetics [109, 110].
The multivalency of SCK-Nps allows flexible radiolabeling ( 64 Cu, 76 br, 124 I, and 18 f)
for peT applications. by conducting DOTA conjugation prior to nanoparticle assem-
bly, the amount of DOTA accessible for 64 Cu labeling can be accurately controlled
with more than 400 copies per SCK, leading to a specific activity greater than
1.48 × 10 7 bq/µg [111]. A novel strategy based on metal-free “click” chemistry has
been developed for the 64 Cu radiolabeling of SCKs. In contrast to the Cu(I)-catalyzed
click chemistry, this metal-free strategy improves 64 Cu labeling of the core of the
nanoparticles due to the high click efficiency. When 1.85 gbq of 64 Cu was used for
radiolabeling of the SCK-Nps containing 10% in-core azides, the specific activity
could be up to 3.61 × 10 13 bq/µmol [112], indicating the great potential of this “click”
labeling strategy for peT imaging.
Another type of core-shell, starlike, or comblike copolymer can be prepared
with nitroxide-mediated living radical polymerization to create defined sizes and