Radio-labeled Nanoparticles for Biomedical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 201

morphologies. In one example, the chelator DOTA was placed in an internal, hydro-
philic environment allowing efficient 64 Cu radiolabeling to make a protected and
high specific activity nanoscopic imaging probe. biodistribution studies showed a
distinct correlation between the length of peg grafts and the in vivo circulation
time; with increased peg chain length, increased blood retention and reduced ReS
uptake were observed [113]. furthermore, the cargo loading capacity of this type
of nanoparticle can be adjusted while retaining comparable physicochemical prop-
erties. In a recent study, varying amounts of RgD peptide (5-50% RgD) were
accurately conjugated to the shell of comblike nanoparticles for targeting α v β 3
integrin, and these RgD-combs all maintained similar sizes and radiolabeling
specific activities [114, 115]. In vitro studies of RgD-combs showed positive
correlation between RgD peptide loading and uptake in α v β 3 integrin-positive
U87mg glioblastoma cells, demonstrating the importance of controlled conjugation
of targeting groups [115]. further, the comb nanoparticles were conjugated with
C-type atrial natriuretic factor (CANf) to target the natriuretic peptide clearance
receptor (NpRC) in a mouse angiogenesis model. by controlling the number of
DOTA conjugations, high specific activity (5.4 ± 1.2 gbq/nmol) 64 Cu radiolabeling
could be achieved, ensuring the trace administration of 64 Cu-DOTA-CANf-comb
(7 pmol) for imaging studies. peT images showed significantly higher standardized
uptake values (SUVs) at angiogenesis sites created by hind limb ischemia compared
to contralateral control sites. more importantly, the SUVs of 64 Cu-DOTA-CANf-
comb were 3.4 times higher than those obtained with DOTA-CANf peptide tracer
and about triple those from the nontargeted 64 Cu-DOTA-comb, demonstrating the
superiority of a multivalent nanoprobe over the corresponding monovalent CANf
peptide for in vivo molecular targeting [116].
In developing nanoparticles for targeted drug delivery, key considerations
include controlled-release kinetics, bioavailability, and reduced toxicity. This has
led to active research in biodegradable nanoparticles [117-119]. Compared to their
inorganic counterparts, polymeric nanoparticles can be prepared with biodegradable
cores or cross-linkers for programmed release of therapeutic payload via enzyme or
pH response degradation. This greatly enhances their biocompatibility and makes
them candidates for targeted diagnosis and drug delivery. A core-shell biodegrad-
able dendritic nanoprobe labeled with 76 br has been prepared for targeting α v β 3 inte-
grins expressed in a mouse angiogenesis model. The controlled introduction of
targeting CRgDC peptide to the shell resulted in a 50-fold enhancement of in vitro
binding affinity to α v β 3 integrins relative to the monovalent RgD peptide alone. In
vivo , specific targeting to α v β 3 was observed with the targeted nanoprobes demon-
strating a six-fold increase of receptor-mediated endocytosis at the injured site com-
pared to the control nanoprobes [23].
Due to fDA approval for human use, the potential of poly(lactide-co-glycolide)-
based biodegradable nanoparticles has been assessed for peT imaging [120].
Recently, various materials such as poly(lactide-co-glycolide), polyacrylates, and
polyacrylamide have been used in the formulation of biodegradable nanoparticles
[121-124]. In contrast to hydrophobic materials, polyacrylamide-based hydrogels
offer excellent biocompatibility and hydrophobicity. They are also strongly endosome